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8524816 | 8524816 | [
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"id": "8524816__text",
"type": "abstract",
"text": [
"Inhibition of NF-AT-dependent transcription by NF-kappa B: implications for differential gene expression in T helper cell subsets. \nActivation of individual CD4+ T cells results in differential lymphokine expression: interleukin 2 (IL-2) is preferentially produced by T helper type 1 (TH1) cells, which are involved in cell-mediated immune responses, whereas IL-4 is synthesized by TH2 cells, which are essential for humoral immunity. The Ca(2+)-dependent factor NF-ATp plays a key role in the inducible transcription of both these lymphokine genes. However, while IL2 expression requires the contribution of Ca(2+)- and protein kinase C-dependent signals, we report that activation of human IL4 transcription through the Ca(2+)-dependent pathway is diminished by protein kinase C stimulation in Jurkat T cells. This phenomenon is due to mutually exclusive binding of NF-ATp and NF-kappa B to the P sequence, an element located 69 bp upstream of the IL4 transcription initiation site. Human IL4 promoter-mediated transcription is downregulated in Jurkat cells stimulated with the NF-kappa B-activating cytokine tumor necrosis factor alpha and suppressed in RelA-overexpressing cells. In contrast, protein kinase C stimulation or RelA overexpression does not affect the activity of a human IL4 promoter containing a mouse P sequence, which is a higher-affinity site for NF-ATp and a lower-affinity site for RelA. Thus, competition between two general transcriptional activators, RelA and NF-ATp, mediates the inhibitory effect of protein kinase C stimulation on IL4 expression and may contribute to differential gene expression in TH cells. "
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}
] | [] |
9007200 | 9007200 | [
{
"id": "9007200__text",
"type": "abstract",
"text": [
"V3 loop of human immunodeficiency virus type 1 suppresses interleukin 2-induced T cell growth [published erratum appears in AIDS Res Hum Retroviruses 1997 May 1;13(7):633] \nWe tested the effect of three linear or two loop peptides derived from the V3 region of the HTLV-III BH10 clone or the SF2 strain of human immunodeficiency virus type 1 on IL-2-driven T cell proliferation. V3-BH10, which consists of 42 amino acids and has a loop structure, suppressed IL-2-driven proliferation of all IL-2-dependent cells [Kit225, ED-40515(+), KT-3, 7-day PHA-blasts, and fresh peripheral blood mononuclear cells] tested, whereas it did not suppress the cell growth of IL-2-independent cell lines (Hut102, Molt-4, and Jurkat). This suppressive effect was also seen in IL-2-driven cell growth of CD8-positive lymphocytes purified from 7-day PHA-blasts, indicating that CD4 molecules were not required for the suppression. The treatment with anti-V3 loop monoclonal antibody (902 antibody) completely abolished the suppressive effect of V3-BH10. In addition, V3-BH10 generated the arrest of Kit225 cells and also purified CD8-positive lymphocytes in G1 phase in the presence of IL-2. Neither chromatin condensation nor DNA fragmentation was detected in Kit225 cells cultured with V3-BH10 and IL-2. V3-BH10 neither blocked radiolabeled IL-2 binding to IL-2 receptors nor affected tyrosyl phosphorylation of several cellular proteins (p120, p98, p96, p54, and p38), which is immediately induced by IL-2 stimulation. However, V3-BH10 enhanced IL-2-induced mRNA expression of c-fos but not c-myc or junB. Thus, the binding of V3 loop of gp120 to the cell surface molecule(s) appears to affect intracellular IL-2 signaling, which leads to the suppression of IL-2-induced T cell growth. "
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"id": "9007200_T22",
"type": "Protein",
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"IL-2"
],
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[
1691,
1695
]
],
"normalized": []
},
{
"id": "9007200_T23",
"type": "Protein",
"text": [
"IL-2"
],
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[
1741,
1745
]
],
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},
{
"id": "9007200_T27",
"type": "Entity",
"text": [
"tyrosyl"
],
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[
1367,
1374
]
],
"normalized": []
},
{
"id": "9007200_T34",
"type": "Entity",
"text": [
"V3 loop"
],
"offsets": [
[
1610,
1617
]
],
"normalized": []
}
] | [
{
"id": "9007200_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocked"
],
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1302,
1309
]
]
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"role": "Theme",
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}
]
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"binding"
],
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1328,
1335
]
]
},
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{
"role": "Theme",
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}
]
},
{
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"affected"
],
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1358,
1366
]
]
},
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"role": "Theme",
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],
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1358,
1366
]
]
},
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"role": "Theme",
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]
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],
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1358,
1366
]
]
},
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"role": "Theme",
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}
]
},
{
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],
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1358,
1366
]
]
},
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"role": "Theme",
"ref_id": "9007200_E13"
}
]
},
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"affected"
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1358,
1366
]
]
},
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"role": "Theme",
"ref_id": "9007200_E14"
}
]
},
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"phosphorylation"
],
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1375,
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]
]
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"role": "Theme",
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},
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1375,
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]
]
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"role": "Theme",
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],
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1375,
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]
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"role": "Theme",
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],
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1375,
1390
]
]
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"role": "Theme",
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"id": "9007200_E12",
"type": "Phosphorylation",
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"text": [
"phosphorylation"
],
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1375,
1390
]
]
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"arguments": [
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"role": "Theme",
"ref_id": "9007200_T14"
},
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"role": "Site",
"ref_id": "9007200_T27"
}
]
},
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"id": "9007200_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
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[
1473,
1480
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9007200_E9"
},
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"role": "Cause",
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}
]
},
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"id": "9007200_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
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1473,
1480
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "9007200_E10"
},
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"role": "Cause",
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}
]
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"id": "9007200_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
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[
1473,
1480
]
]
},
"arguments": [
{
"role": "Theme",
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},
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"id": "9007200_E16",
"type": "Positive_regulation",
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"text": [
"induced"
],
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[
1473,
1480
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9007200_E12"
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"role": "Cause",
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}
]
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"id": "9007200_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1473,
1480
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9007200_E8"
},
{
"role": "Cause",
"ref_id": "9007200_T16"
}
]
},
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"id": "9007200_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
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1519,
1527
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "9007200_E23"
}
]
},
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"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
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[
1519,
1527
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9007200_E21"
}
]
},
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"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
1519,
1527
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9007200_E22"
}
]
},
{
"id": "9007200_E21",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1533,
1540
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9007200_E25"
},
{
"role": "Cause",
"ref_id": "9007200_T17"
}
]
},
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"id": "9007200_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1533,
1540
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9007200_E24"
},
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}
]
},
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"id": "9007200_E23",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
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[
1533,
1540
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9007200_E26"
},
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"role": "Cause",
"ref_id": "9007200_T17"
}
]
},
{
"id": "9007200_E24",
"type": "Transcription",
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"text": [
"mRNA expression"
],
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1541,
1556
]
]
},
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"role": "Theme",
"ref_id": "9007200_T19"
}
]
},
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"text": [
"mRNA expression"
],
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1541,
1556
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]
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}
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"type": "Transcription",
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"text": [
"mRNA expression"
],
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1541,
1556
]
]
},
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"role": "Theme",
"ref_id": "9007200_T20"
}
]
},
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"type": "Binding",
"trigger": {
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"binding"
],
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[
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]
]
},
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"role": "Theme",
"ref_id": "9007200_T21"
},
{
"role": "Site",
"ref_id": "9007200_T34"
}
]
}
] | [] | [] |
9277450 | 9277450 | [
{
"id": "9277450__text",
"type": "abstract",
"text": [
"Surfactant protein A activates NF-kappa B in the THP-1 monocytic cell line. \nThe expression of many genes for which products are involved in inflammation is controlled by the transcriptional regulator nuclear factor (NF)-kappa B. Because surfactant protein (SP) A is involved in local host defense in the lung and alters immune cell function by modulating the expression of proinflammatory cytokines as well as surface proteins involved in inflammation, we hypothesized that SP-A exerts its action, at least in part, via activation of NF-kappa B. We used gel shift assays to determine whether SP-A activated NF-kappa B in the THP-1 cell line, a human monocytic cell line. Activation of NF-kappa B in THP-1 cells by SP-A doses as low as 1 microgram/ml occurred within 30 min of SP-A treatment, peaked at 60 min, and then declined. This activation is inhibited by known inhibitors of NF-kappa B or by simultaneous treatment of the cells with surfactant lipids. Moreover, the NF-kappa B inhibitors blocked SP-A-dependent increases in tumor necrosis factor-alpha mRNA levels. These observations suggest a mechanism by which SP-A plays a role in the pathogenesis of some lung conditions and point to potential therapeutic measures that could be used to prevent SP-A induced inflammation in the lung. "
],
"offsets": [
[
0,
1295
]
]
}
] | [
{
"id": "9277450_T1",
"type": "Protein",
"text": [
"Surfactant protein A"
],
"offsets": [
[
0,
20
]
],
"normalized": []
},
{
"id": "9277450_T2",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
1031,
1058
]
],
"normalized": []
}
] | [
{
"id": "9277450_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocked"
],
"offsets": [
[
995,
1002
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9277450_E2"
}
]
},
{
"id": "9277450_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"increases"
],
"offsets": [
[
1018,
1027
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9277450_T2"
}
]
}
] | [] | [] |
8314792 | 8314792 | [
{
"id": "8314792__text",
"type": "abstract",
"text": [
"Comparative analysis of NFAT (nuclear factor of activated T cells) complex in human T and B lymphocytes. \nNuclear factor of activated T cells (NFAT) is a transcriptional activator that binds to sequences in the interleukin-2 (IL-2) promoter and is thought to be largely responsible for the T cell-specific inducibility of IL-2 expression. Electrophoretic mobility shift assays (EMSA) showed that specific NFAT binding activity could also be induced in human B cells. The B cell NFAT complex, however, was not functional, since it failed to activate transcription from an NFAT-driven chloramphenicol acetyltransferase (CAT) construct. Competition with an AP-1 motif or with anti-Jun and anti-Fos antibodies abolished binding to the NFAT motif in both T and B cells, indicating that Jun and Fos are critical for NFAT complex formation in both cell types. Purified recombinant Jun and Fos proteins failed to bind directly to the NFAT motif. However, when combined with unstimulated B or T cell extracts, full-length, but not truncated, Jun/Fos heterodimers were able to form an NFAT complex, indicating the presence of a constitutively expressed nuclear factor(s) in B and T cells necessary for the formation of the NFAT complex in both cell types. An NFAT oligonucleotide carrying mutations in the 5' purine-rich part of the NFAT sequence failed to form a complex and to compete with the wild type motif for NFAT complex formation in both T and B cells. We therefore propose a model whereby a core NFAT complex consisting of Jun, Fos, and a constitutive nuclear factor is formed in both T and B cells, but an additional factor and/or post-translational modification of a factor, missing in B cells, might be required for transactivation by NFAT. "
],
"offsets": [
[
0,
1744
]
]
}
] | [
{
"id": "8314792_T1",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
211,
224
]
],
"normalized": []
},
{
"id": "8314792_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
226,
230
]
],
"normalized": []
},
{
"id": "8314792_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
322,
326
]
],
"normalized": []
},
{
"id": "8314792_T4",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
"offsets": [
[
583,
616
]
],
"normalized": []
},
{
"id": "8314792_T5",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
618,
621
]
],
"normalized": []
},
{
"id": "8314792_T7",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
232,
240
]
],
"normalized": []
}
] | [
{
"id": "8314792_E1",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
185,
190
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8314792_T1"
},
{
"role": "Site",
"ref_id": "8314792_T7"
}
]
},
{
"id": "8314792_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"responsible"
],
"offsets": [
[
270,
281
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8314792_E3"
}
]
},
{
"id": "8314792_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"inducibility"
],
"offsets": [
[
306,
318
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8314792_E4"
}
]
},
{
"id": "8314792_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
327,
337
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8314792_T3"
}
]
},
{
"id": "8314792_E5",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
410,
426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8314792_T1"
},
{
"role": "Site",
"ref_id": "8314792_T7"
}
]
},
{
"id": "8314792_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
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[
441,
448
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8314792_E5"
}
]
},
{
"id": "8314792_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"activate"
],
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[
540,
548
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8314792_E8"
}
]
},
{
"id": "8314792_E8",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
549,
562
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8314792_T4"
}
]
}
] | [
{
"id": "8314792_1",
"entity_ids": [
"8314792_T1",
"8314792_T2"
]
},
{
"id": "8314792_2",
"entity_ids": [
"8314792_T4",
"8314792_T5"
]
}
] | [] |
8523529 | 8523529 | [
{
"id": "8523529__text",
"type": "abstract",
"text": [
"Protein kinase C-zeta mediates NF-kappa B activation in human immunodeficiency virus-infected monocytes. \nThe molecular mechanisms regulating human immunodeficiency virus (HIV) persistence in a major cell reservoir such as the macrophage remain unknown. NF-kappa B is a transcription factor involved in the regulation of the HIV long terminal repeat and is selectively activated following HIV infection of human macrophages. Although little information as to what signal transduction pathways mediate NF-kappa B activation in monocytes-macrophages is available, our previous work indicated that classical protein kinase C (PKC) isoenzymes were not involved in the HIV-mediated NF-kappa B activation. In this study, we have focused on atypical PKC isoenzymes. PKC-zeta belongs to this family and is known to be an important step in NF-kappa B activation in other cell systems. Immunoblotting experiments with U937 cells demonstrate that PKC-zeta is present in these cells, and its expression can be downmodulated by antisense oligonucleotides (AO). The HIV-mediated NF-kappa B activation is selectively reduced by AO to PKC-zeta. In addition, cotransfection of a negative dominant molecule of PKC-zeta (PKC-zeta mut) with NF-kappa B-dependent reporter genes selectively inhibits the HIV- but not phorbol myristate acetate- or lipopolysaccharide-mediated activation of NF-kappa B. That PKC-zeta is specific in regulating NF-kappa B is concluded from the inability of PKC-zeta(mut) to interfere with the basal or phorbol myristate acetate-inducible CREB- or AP1-dependent transcriptional activity. Lastly, we demonstrate a selective inhibition of p24 production by HIV-infected human macrophages when treated with AO to PKC-zeta. Altogether, these results suggest that atypical PKC isoenzymes, including PKC-zeta, participate in the signal transduction pathways by which HIV infection results in the activation of NF-kappa B in human monocytic cells and macrophages. "
],
"offsets": [
[
0,
1964
]
]
}
] | [
{
"id": "8523529_T1",
"type": "Protein",
"text": [
"Protein kinase C-zeta"
],
"offsets": [
[
0,
21
]
],
"normalized": []
},
{
"id": "8523529_T2",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
759,
767
]
],
"normalized": []
},
{
"id": "8523529_T3",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
936,
944
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],
"normalized": []
},
{
"id": "8523529_T4",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
1119,
1127
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],
"normalized": []
},
{
"id": "8523529_T5",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
1192,
1200
]
],
"normalized": []
},
{
"id": "8523529_T6",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
1202,
1210
]
],
"normalized": []
},
{
"id": "8523529_T7",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
1384,
1392
]
],
"normalized": []
},
{
"id": "8523529_T8",
"type": "Protein",
"text": [
"PKC-zeta"
],
"offsets": [
[
1465,
1473
]
],
"normalized": []
},
{
"id": "8523529_T9",
"type": "Protein",
"text": [
"CREB"
],
"offsets": [
[
1546,
1550
]
],
"normalized": []
}
] | [
{
"id": "8523529_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"present"
],
"offsets": [
[
948,
955
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8523529_T3"
}
]
},
{
"id": "8523529_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"downmodulated"
],
"offsets": [
[
998,
1011
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8523529_E1"
}
]
},
{
"id": "8523529_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"cotransfection"
],
"offsets": [
[
1142,
1156
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8523529_T5"
}
]
}
] | [] | [] |
8645254 | 8645254 | [
{
"id": "8645254__text",
"type": "abstract",
"text": [
"Abundant expression of erythroid transcription factor P45 NF-E2 mRNA in human peripheral granurocytes. \nTranscription factor NF-E2 is crucial for regulation of erythroid-specific gene expression. p45 subunit of NF-E2 contains a basic-leucine zipper domain and dimerizes with the small Maf family protein to form functional NF-E2 complex. While p45 expression was shown to be restricted to erythroid cells, megakaryocytes and mast cells in hematopoietic lineage, we found in this study that p45 mRNA is abundantly transcribed in the granulocyte fraction of human peripheral blood cells. As neutrophils occupy approximately 92% of the cells in granulocyte fraction of human peripheral blood cells. As neutrophils occupy approximately 92% of the cells in this fraction, the cells expressing p45 is most likely to be neutrophils. p45 mRNA is also expressed in HL-60 promyelocytes, albeit the expression level is much lower than that of the granulocyte fraction. HL-60 cells were found to express mafK mRNA, indicating the presence of genuine NF-E2 complex in the cells. Although p45 mRNA is transcribed from two different promoters, aNF-E2 promoter and fNF-E2 promoter, in erythroid and megakaryocytic lineage cells, p45 mRNA is transcribed only from aNF-E2 promoter. The expression of p45 megakaryocytic lineage cells, p45 mRNA is transcribed only from aNF-E2 promoter. The expression of p45 mRNA in the neutrophils declined rapidly after transfer of the cells to in vitro culture and G-CSF could not sustain the expression from the down-regulation, suggesting the E2 may also participate in the regulation of neutrophil-specific gene expression. "
],
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[
0,
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],
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196,
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1282,
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1482,
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}
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"role": "Theme",
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"role": "Theme",
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"role": "Theme",
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"from"
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},
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"role": "Theme",
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"expression"
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]
]
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"role": "Theme",
"ref_id": "8645254_T10"
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{
"id": "8645254_E14",
"type": "Transcription",
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"text": [
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],
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1328,
1339
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "8645254_T11"
}
]
},
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"id": "8645254_E15",
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"text": [
"from"
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1345,
1349
]
]
},
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"role": "Theme",
"ref_id": "8645254_E14"
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},
{
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"text": [
"expression"
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "8645254_T12"
}
]
},
{
"id": "8645254_E17",
"type": "Negative_regulation",
"trigger": {
"text": [
"declined"
],
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1413,
1421
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "8645254_E16"
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]
},
{
"id": "8645254_E18",
"type": "Negative_regulation",
"trigger": {
"text": [
"sustain"
],
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1498,
1505
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "8645254_E17"
},
{
"role": "Cause",
"ref_id": "8645254_T13"
}
]
}
] | [] | [] |
7981603 | 7981603 | [
{
"id": "7981603__text",
"type": "abstract",
"text": [
"Glucocorticoid-induced apoptosis of lymphoid cells. \nThe induction of cell death in lymphoid cells by glucocorticoids is one of the earliest and most thoroughly studied models of apoptosis. Although the exact mechanism by which apoptosis occurs in lymphocytes is unknown many biochemical and molecular changes have been shown to occur in these cells in response to glucocorticoids. The role of chromatin degradation and endonucleases in the apoptotic process has been closely studied, as well as the involvement of several oncogenes in glucocorticoid-induced cell lysis. In addition, the clinical importance of glucocorticoid-induced apoptosis in the treatment of lymphoid neoplasms has recently received increased attention. "
],
"offsets": [
[
0,
726
]
]
}
] | [] | [] | [] | [] |
10331989 | 10331989 | [
{
"id": "10331989__text",
"type": "abstract",
"text": [
"Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene. \nThe lineage-restricted transcription factor GATA-1 is required for differentiation of erythroid and megakaryocytic cells. We have localized a 317 base pair cis-acting regulatory element, HS I, associated with a hematopoietic-specific DNase I hypersensitive site, which lies approx. 3.7 kilobases upstream of the murine hematopoietic-specific GATA-1 IE promoter. HS I directs high-level expression of reporter GATA-1/lacZ genes to primitive and definitive erythroid cells and megakaryocytes in transgenic mice. Comparative sequence analysis of HS I between human and mouse shows approx. 63% nucleotide identity with a more conserved core of 169 base pairs (86% identity). This core contains a GATA site separated by 10 base pairs from an E-box motif. The composite motif binds a multi-protein hematopoietic-specific transcription factor complex which includes GATA-1, SCL/tal-1, E2A, Lmo2 and Ldb-1. Point mutations of the GATA site abolishes HS I function, whereas mutation of the E-box motif still allows reporter gene expression in both lineages. Strict dependence of HS I activity on a GATA site implies that assembly of a protein complex containing a GATA-factor, presumably GATA-1 or GATA-2, is critical to activating or maintaining its function. Further dissection of the 317 base pair region demonstrates that, whereas all 317 base pairs are required for expression in megakaryocytes, only the 5' 62 base pairs are needed for erythroid-specific reporter expression. These findings demonstrate differential lineage requirements for expression within the HS I element. "
],
"offsets": [
[
0,
1717
]
]
}
] | [
{
"id": "10331989_T1",
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],
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129,
135
]
],
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{
"id": "10331989_T2",
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],
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187,
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]
],
"normalized": []
},
{
"id": "10331989_T3",
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"GATA-1"
],
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485,
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]
],
"normalized": []
},
{
"id": "10331989_T4",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
552,
558
]
],
"normalized": []
},
{
"id": "10331989_T5",
"type": "Protein",
"text": [
"lacZ"
],
"offsets": [
[
559,
563
]
],
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},
{
"id": "10331989_T6",
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],
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]
],
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},
{
"id": "10331989_T7",
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],
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1010,
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]
],
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},
{
"id": "10331989_T8",
"type": "Protein",
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"tal-1"
],
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[
1014,
1019
]
],
"normalized": []
},
{
"id": "10331989_T9",
"type": "Protein",
"text": [
"E2A"
],
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[
1021,
1024
]
],
"normalized": []
},
{
"id": "10331989_T10",
"type": "Protein",
"text": [
"Lmo2"
],
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1026,
1030
]
],
"normalized": []
},
{
"id": "10331989_T11",
"type": "Protein",
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],
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1035,
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]
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},
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"id": "10331989_T12",
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],
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1322,
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"id": "10331989_T13",
"type": "Protein",
"text": [
"GATA-2"
],
"offsets": [
[
1332,
1338
]
],
"normalized": []
}
] | [
{
"id": "10331989_E1",
"type": "Positive_regulation",
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"text": [
"requirements"
],
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19,
31
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10331989_E2"
}
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"expression"
],
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36,
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]
},
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"role": "Theme",
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}
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"text": [
"directs"
],
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510,
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]
]
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"role": "Theme",
"ref_id": "10331989_E4"
}
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],
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"role": "Theme",
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}
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"id": "10331989_E5",
"type": "Binding",
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"binds"
],
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913,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10331989_T6"
}
]
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"id": "10331989_E6",
"type": "Binding",
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"binds"
],
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913,
918
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10331989_T9"
}
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},
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"id": "10331989_E7",
"type": "Binding",
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"text": [
"binds"
],
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913,
918
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "10331989_T7"
}
]
},
{
"id": "10331989_E8",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
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[
913,
918
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10331989_T10"
}
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},
{
"id": "10331989_E9",
"type": "Binding",
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"text": [
"binds"
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913,
918
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]
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"role": "Theme",
"ref_id": "10331989_T11"
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{
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"type": "Binding",
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"role": "Theme",
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"type": "Binding",
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1255,
1284
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10331989_T12"
}
]
}
] | [
{
"id": "10331989_1",
"entity_ids": [
"10331989_T7",
"10331989_T8"
]
}
] | [] |
9195127 | 9195127 | [
{
"id": "9195127__text",
"type": "abstract",
"text": [
"Biphasic control of NF-kappa B activation induced by the triggering of HLA-DR antigens expressed on B cells. \nThe regulation of NF-kappa B activation following the triggering of HLA-DR antigens by mAb L243 has been studied at various times in Raji cells. Electrophoretic mobility shift assays demonstrated a strong increase of NF-kappa B DNA binding after triggering of HLA-DR antigens. Using TNF-alpha-activity neutralizing antibodies, the authors demonstrated that the upregulation of NF-kappa B was found to depend, at later time point, on an autocrine effect of TNF-alpha secreted following triggering of HLA-DR antigens. In contrast, it was found to be TNF-alpha independent in the early time point. Moreover, the upregulation of NF-kappa B binding activity is regulated by the triggering of selected epitopes of HLA-DR antigens. In fact, mAb L243 but not the staphylococcal superantigens, staphylococcal exotoxin toxic shock syndrome toxin-I or staphylococcal enterotoxin B, regulate the NF-kappa B binding activity. "
],
"offsets": [
[
0,
1023
]
]
}
] | [
{
"id": "9195127_T1",
"type": "Protein",
"text": [
"TNF-alpha"
],
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[
393,
402
]
],
"normalized": []
},
{
"id": "9195127_T2",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
566,
575
]
],
"normalized": []
},
{
"id": "9195127_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
658,
667
]
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"normalized": []
},
{
"id": "9195127_T4",
"type": "Protein",
"text": [
"toxic shock syndrome toxin-I"
],
"offsets": [
[
919,
947
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"normalized": []
},
{
"id": "9195127_T5",
"type": "Protein",
"text": [
"staphylococcal enterotoxin B"
],
"offsets": [
[
951,
979
]
],
"normalized": []
}
] | [
{
"id": "9195127_E1",
"type": "Localization",
"trigger": {
"text": [
"secreted"
],
"offsets": [
[
576,
584
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9195127_T2"
}
]
},
{
"id": "9195127_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"following"
],
"offsets": [
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585,
594
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9195127_E1"
}
]
}
] | [] | [] |
9047239 | 9047239 | [
{
"id": "9047239__text",
"type": "abstract",
"text": [
"A T cell-specific enhancer in the interleukin-3 locus is activated cooperatively by Oct and NFAT elements within a DNase I-hypersensitive site. \nInterleukin-3 (IL-3) is a cytokine that is expressed primarily in activated T cells. Here we identified an inducible T cell-specific enhancer 14 kb upstream of the IL-3 gene that responded to activation of T cell receptor signaling pathways. The IL-3 enhancer spanned an inducible cyclosporin A-sensitive DNase I-hypersensitive site found only in T cells. Four NFAT-like elements exist within the enhancer. The two most active NFAT-like elements were located at the center of the DNase I-hypersensitive site. One of these NFAT-like elements encompassed overlapping Oct- and NFATp/c-binding sites, which functioned in a highly synergistic manner. We suggest that the T cell-specific expression of the IL-3 gene is partly controlled through the enhancer by cooperation between Oct and NFAT family proteins. "
],
"offsets": [
[
0,
950
]
]
}
] | [
{
"id": "9047239_T1",
"type": "Protein",
"text": [
"interleukin-3"
],
"offsets": [
[
34,
47
]
],
"normalized": []
},
{
"id": "9047239_T2",
"type": "Protein",
"text": [
"Interleukin-3"
],
"offsets": [
[
145,
158
]
],
"normalized": []
},
{
"id": "9047239_T3",
"type": "Protein",
"text": [
"IL-3"
],
"offsets": [
[
160,
164
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],
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},
{
"id": "9047239_T4",
"type": "Protein",
"text": [
"IL-3"
],
"offsets": [
[
309,
313
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],
"normalized": []
},
{
"id": "9047239_T5",
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"text": [
"IL-3"
],
"offsets": [
[
391,
395
]
],
"normalized": []
},
{
"id": "9047239_T6",
"type": "Protein",
"text": [
"IL-3"
],
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845,
849
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},
{
"id": "9047239_T10",
"type": "Entity",
"text": [
"enhancer"
],
"offsets": [
[
396,
404
]
],
"normalized": []
}
] | [
{
"id": "9047239_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated cooperatively"
],
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57,
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]
]
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"expressed"
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188,
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]
]
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"role": "Theme",
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}
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"inducible"
],
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252,
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]
]
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"role": "Theme",
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"role": "Theme",
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"ref_id": "9047239_T10"
}
]
}
] | [
{
"id": "9047239_1",
"entity_ids": [
"9047239_T2",
"9047239_T3"
]
}
] | [] |
7826623 | 7826623 | [
{
"id": "7826623__text",
"type": "abstract",
"text": [
"T-cell functional regions of the human IL-3 proximal promoter. \nThe human interleukin-3 (IL-3) gene is expressed almost exclusively in activated T cells. Its expression is regulated at both the transcriptional and post-transcriptional level. We have previously shown that treatment of Jurkat T cells with phytohemaglutinin (PHA) and the phorbol ester, PMA, activated transcription initiation from the IL-3 gene. To define the regions of the gene required for transcription activation, we generated a series of reporter constructs containing different regions of the IL-3 gene 5' and 3' flanking sequences. Both positive and negative regulatory elements were identified in the proximal 5' flanking region of the IL-3 gene. The promoter region between -173 and -60 contained the strongest activating elements. The transcription factor AP-1 could bind to this positive activator region of the promoter. We also examined the function of the IL-3 CK-1/CK-2 elements that are present in many cytokine genes and found that they acted as a repressor of basal level expression when cloned upstream of a heterologous promoter but were also inducible by PMA/PHA. "
],
"offsets": [
[
0,
1152
]
]
}
] | [
{
"id": "7826623_T1",
"type": "Protein",
"text": [
"IL-3"
],
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[
39,
43
]
],
"normalized": []
},
{
"id": "7826623_T2",
"type": "Protein",
"text": [
"interleukin-3"
],
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74,
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]
],
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},
{
"id": "7826623_T3",
"type": "Protein",
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"IL-3"
],
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89,
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]
],
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},
{
"id": "7826623_T4",
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],
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305,
322
]
],
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},
{
"id": "7826623_T5",
"type": "Protein",
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"PHA"
],
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[
324,
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]
],
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{
"id": "7826623_T6",
"type": "Protein",
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"IL-3"
],
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401,
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]
],
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"id": "7826623_T7",
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"IL-3"
],
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{
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]
],
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]
],
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},
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"id": "7826623_T10",
"type": "Protein",
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"CK-1"
],
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]
],
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},
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"id": "7826623_T11",
"type": "Protein",
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"CK-2"
],
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]
],
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},
{
"id": "7826623_T12",
"type": "Protein",
"text": [
"PHA"
],
"offsets": [
[
1147,
1150
]
],
"normalized": []
}
] | [
{
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"expressed"
],
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103,
112
]
]
},
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]
},
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"ref_id": "7826623_T3"
}
]
},
{
"id": "7826623_E3",
"type": "Regulation",
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"regulated"
],
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172,
181
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "7826623_E2"
}
]
},
{
"id": "7826623_E4",
"type": "Regulation",
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"regulated"
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172,
181
]
]
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"role": "Theme",
"ref_id": "7826623_E5"
}
]
},
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194,
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]
]
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"role": "Theme",
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}
]
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"id": "7826623_E6",
"type": "Positive_regulation",
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"activated"
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]
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"role": "Theme",
"ref_id": "7826623_E7"
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],
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"type": "Positive_regulation",
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{
"role": "Cause",
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]
}
] | [
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"7826623_T3"
]
},
{
"id": "7826623_2",
"entity_ids": [
"7826623_T4",
"7826623_T5"
]
}
] | [] |
10327050 | 10327050 | [
{
"id": "10327050__text",
"type": "abstract",
"text": [
"Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F. \nInitiation of DNA replication requires the function of MCM gene products, which participate in ensuring that DNA replication occurs only once in the cell cycle. Expression of all mammalian genes of the MCM family is induced by growth stimulation, unlike yeast, and the mRNA levels peak at G1/S boundary. In this study, we examined the transcriptional activities of isolated human MCM gene promoters. Human MCM5 and MCM6 promoters with mutation in the E2F sites failed in promoter regulation following serum stimulation and exogenous E2F expression. In addition, we identified a novel E2F-like sequence in human MCM6 promoter which cooperates with the authentic E2F sites in E2F-dependent regulation. Forced expression of E2F1 could induce expression of all members of the endogenous MCM genes in rat embryonal fibroblast REF52 cells. Our results demonstrated that the growth-regulated expression of mammalian MCM5 and MCM6 genes, and presumably other MCM members, is primarily regulated by E2F through binding to multiple E2F sites in the promoters. "
],
"offsets": [
[
0,
1159
]
]
}
] | [
{
"id": "10327050_T1",
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"MCM5"
],
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[
46,
50
]
],
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},
{
"id": "10327050_T2",
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"MCM6"
],
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55,
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]
],
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},
{
"id": "10327050_T3",
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"MCM5"
],
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515,
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]
],
"normalized": []
},
{
"id": "10327050_T4",
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"MCM6"
],
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524,
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]
],
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},
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"id": "10327050_T5",
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"MCM6"
],
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720,
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]
],
"normalized": []
},
{
"id": "10327050_T6",
"type": "Protein",
"text": [
"E2F1"
],
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830,
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]
],
"normalized": []
},
{
"id": "10327050_T7",
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],
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},
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"id": "10327050_T8",
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"MCM6"
],
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},
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529,
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]
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},
{
"id": "10327050_T15",
"type": "Entity",
"text": [
"E2F-like sequence"
],
"offsets": [
[
693,
710
]
],
"normalized": []
}
] | [
{
"id": "10327050_E1",
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12,
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22,
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}
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]
},
"arguments": [
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"role": "Theme",
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},
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"mediated"
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"id": "10327050_E7",
"type": "Negative_regulation",
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570,
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"role": "Theme",
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},
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"id": "10327050_E8",
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"text": [
"failed"
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570,
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]
]
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"arguments": [
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"role": "Theme",
"ref_id": "10327050_E9"
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"regulation"
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"role": "Theme",
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"role": "Theme",
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"regulated"
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"text": [
"regulated"
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]
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"arguments": [
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"role": "Theme",
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}
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"id": "10327050_E16",
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"text": [
"expression"
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]
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},
"arguments": [
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"role": "Theme",
"ref_id": "10327050_T7"
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"id": "10327050_E17",
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"expression"
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"arguments": [
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"role": "Theme",
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"id": "10327050_E18",
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"regulated"
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"regulated"
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"regulated"
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"ref_id": "10327050_E16"
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"role": "Cause",
"ref_id": "10327050_E23"
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"id": "10327050_E21",
"type": "Regulation",
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"text": [
"regulated"
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1086,
1095
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]
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"role": "Theme",
"ref_id": "10327050_E17"
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{
"role": "Cause",
"ref_id": "10327050_E22"
}
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},
{
"id": "10327050_E22",
"type": "Binding",
"trigger": {
"text": [
"binding"
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1111,
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},
"arguments": [
{
"role": "Theme",
"ref_id": "10327050_T8"
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},
{
"id": "10327050_E23",
"type": "Binding",
"trigger": {
"text": [
"binding"
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"offsets": [
[
1111,
1118
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10327050_T7"
}
]
}
] | [] | [] |
10200294 | 10200294 | [
{
"id": "10200294__text",
"type": "abstract",
"text": [
"A novel lipopolysaccharide-induced transcription factor regulating tumor necrosis factor alpha gene expression: molecular cloning, sequencing, characterization, and chromosomal assignment. \nLipopolysaccharide (LPS) is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor alpha (TNF-alpha) and other inflammatory mediators. Given the deleterious effects to the host of TNF-alpha, it has been postulated that TNF-alpha gene expression must be tightly regulated. The nature of the nuclear factor(s) that control TNF-alpha gene transcription in humans remains obscure, although NF-kappaB has been suggested. Our previous studies pertaining to macrophage response to LPS identified a novel DNA-binding domain located from -550 to -487 in the human TNF-alpha promoter that contains transcriptional activity, but lacks any known NF-kappaB-binding sites. We have used this DNA fragment to isolate and purify a 60-kDa protein binding to this fragment and obtained its amino-terminal sequence, which was used to design degenerate probes to screen a cDNA library from THP-1 cells. A novel cDNA clone (1.8 kb) was isolated and fully sequenced. Characterization of this cDNA clone revealed that its induction was dependent on LPS activation of THP-1 cells; hence, the name LPS-induced TNF-alpha factor (LITAF). Inhibition of LITAF mRNA expression in THP-1 cells resulted in a reduction of TNF-alpha transcripts. In addition, high level of expression of LITAF mRNA was observed predominantly in the placenta, peripheral blood leukocytes, lymph nodes, and the spleen. Finally, chromosomal localization using fluorescence in situ hybridization revealed that LITAF mapped to chromosome 16p12-16p13.3. Together, these findings suggest that LITAF plays an important role in the activation of the human TNF-alpha gene and proposes a new mechanism to control TNF-alpha gene expression. "
],
"offsets": [
[
0,
1905
]
]
}
] | [
{
"id": "10200294_T1",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
67,
94
]
],
"normalized": []
},
{
"id": "10200294_T2",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
289,
316
]
],
"normalized": []
},
{
"id": "10200294_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
318,
327
]
],
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},
{
"id": "10200294_T4",
"type": "Protein",
"text": [
"TNF-alpha"
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[
408,
417
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],
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},
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"id": "10200294_T5",
"type": "Protein",
"text": [
"TNF-alpha"
],
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447,
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},
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"id": "10200294_T6",
"type": "Protein",
"text": [
"TNF-alpha"
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549,
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},
{
"id": "10200294_T7",
"type": "Protein",
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"TNF-alpha"
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783,
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},
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"id": "10200294_T8",
"type": "Protein",
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"LPS-induced TNF-alpha factor"
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"id": "10200294_T9",
"type": "Protein",
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{
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],
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1682,
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1762,
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{
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1823,
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{
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1878,
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]
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},
{
"id": "10200294_T25",
"type": "Entity",
"text": [
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],
"offsets": [
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725,
743
]
],
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}
] | [
{
"id": "10200294_E1",
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"regulating"
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56,
66
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95,
110
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]
]
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{
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"secretion"
],
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276,
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]
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{
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"expression"
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"resulted in a reduction"
],
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"transcripts"
],
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"role": "Theme",
"ref_id": "10200294_T11"
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"text": [
"high level"
],
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]
]
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"role": "Theme",
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"role"
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]
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"id": "10200294_E19",
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"text": [
"activation"
],
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]
]
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]
]
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] | [
{
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]
},
{
"id": "10200294_2",
"entity_ids": [
"10200294_T2",
"10200294_T3"
]
}
] | [] |
1946356 | 1946356 | [
{
"id": "1946356__text",
"type": "abstract",
"text": [
"Negative regulation of human immunodeficiency virus type 1 expression in monocytes: role of the 65-kDa plus 50-kDa NF-kappa B dimer. \nAlthough monocytic cells can provide a reservoir for viral production in vivo, their regulation of human immunodeficiency virus type 1 (HIV-1) transcription can be either latent, restricted, or productive. These differences in gene expression have not been molecularly defined. In THP-1 cells with restricted HIV expression, there is an absence of DNA-protein binding complex formation with the HIV-1 promoter-enhancer associated with markedly less viral RNA production. This absence of binding was localized to the NF-kappa B region of the HIV-1 enhancer; the 65-kDa plus 50-kDa NF-kappa B heterodimer was preferentially lost. Adding purified NF-kappa B protein to nuclear extracts from cells with restricted expression overcomes this lack of binding. In addition, treatment of these nuclear extracts with sodium deoxycholate restored their ability to form the heterodimer, suggesting the presence of an inhibitor of NF-kappa B activity. Furthermore, treatment of nuclear extracts from these cells that had restricted expression with lipopolysaccharide increased viral production and NF-kappa B activity. Antiserum specific for NF-kappa B binding proteins, but not c-rel-specific antiserum, disrupted heterodimer complex formation. Thus, both NF-kappa B-binding complexes are needed for optimal viral transcription. Binding of the 65-kDa plus 50-kDa heterodimer to the HIV-1 enhancer can be negatively regulated in monocytes, providing one mechanism restricting HIV-1 gene expression. "
],
"offsets": [
[
0,
1620
]
]
}
] | [
{
"id": "1946356_T1",
"type": "Protein",
"text": [
"65-kDa"
],
"offsets": [
[
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102
]
],
"normalized": []
},
{
"id": "1946356_T2",
"type": "Protein",
"text": [
"50-kDa"
],
"offsets": [
[
108,
114
]
],
"normalized": []
},
{
"id": "1946356_T3",
"type": "Protein",
"text": [
"65-kDa"
],
"offsets": [
[
695,
701
]
],
"normalized": []
},
{
"id": "1946356_T4",
"type": "Protein",
"text": [
"50-kDa"
],
"offsets": [
[
707,
713
]
],
"normalized": []
},
{
"id": "1946356_T5",
"type": "Protein",
"text": [
"65-kDa"
],
"offsets": [
[
1466,
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]
],
"normalized": []
},
{
"id": "1946356_T6",
"type": "Protein",
"text": [
"50-kDa"
],
"offsets": [
[
1478,
1484
]
],
"normalized": []
}
] | [
{
"id": "1946356_E1",
"type": "Binding",
"trigger": {
"text": [
"heterodimer"
],
"offsets": [
[
725,
736
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_T3"
},
{
"role": "Theme",
"ref_id": "1946356_T4"
}
]
},
{
"id": "1946356_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"lost"
],
"offsets": [
[
756,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_E1"
}
]
},
{
"id": "1946356_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"overcomes"
],
"offsets": [
[
855,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_E2"
}
]
},
{
"id": "1946356_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"restored"
],
"offsets": [
[
961,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_E1"
}
]
},
{
"id": "1946356_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"disrupted"
],
"offsets": [
[
1326,
1335
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_E1"
}
]
},
{
"id": "1946356_E6",
"type": "Binding",
"trigger": {
"text": [
"Binding"
],
"offsets": [
[
1451,
1458
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_T6"
}
]
},
{
"id": "1946356_E7",
"type": "Binding",
"trigger": {
"text": [
"Binding"
],
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[
1451,
1458
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_T5"
}
]
},
{
"id": "1946356_E8",
"type": "Binding",
"trigger": {
"text": [
"heterodimer"
],
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[
1485,
1496
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_T5"
},
{
"role": "Theme",
"ref_id": "1946356_T6"
}
]
},
{
"id": "1946356_E9",
"type": "Negative_regulation",
"trigger": {
"text": [
"negatively regulated"
],
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1526,
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_E6"
}
]
},
{
"id": "1946356_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"negatively regulated"
],
"offsets": [
[
1526,
1546
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1946356_E7"
}
]
}
] | [] | [] |
9819151 | 9819151 | [
{
"id": "9819151__text",
"type": "abstract",
"text": [
"Transcription factor NF-kappaB regulation of renal fibrosis during ureteral obstruction. \nIrrespective of the etiology, many kidney diseases result in inflammation and fibrosis of the tubulointerstitium, with the subsequent loss of renal function. To initiate any disease process or for any disease process to progress, there must be changes in the transcription of genes within the affected tissue. The nuclear factor-kappa B (NF-kappaB) family of transcription factors regulates genes involved in inflammation, cell proliferation, and cell differentiation. This review discusses the NF-kappaB transcription factor family in general and the association of NF-kappaB activation with cellular/molecular events of renal inflammation and fibrosis. "
],
"offsets": [
[
0,
745
]
]
}
] | [] | [] | [] | [] |
9219058 | 9219058 | [
{
"id": "9219058__text",
"type": "abstract",
"text": [
"Association between expression of intercellular adhesion molecule-1 and integration of human T-cell-leukemia virus type 1 in adult T-cell leukemia cells. \nIt is known that the expression levels of intercellular adhesion molecule-1 (ICAM-1) in adult T cell leukemia(ATL) cells are high, whereas those in T-lymphoid cells are not. In order to investigate the factors that influence the induction of ICAM-1 molecules, Northern blot analysis to measure the expression level of ICAM-1 mRNAs and Southern blot hybridization to analyze the integration of human T-cell-leukemia virus type 1 (HTLV-1) provirus were done. The levels of ICAM-1 mRNA expression of ATL cells were generally higher than those of T-lymphoid cells. However, ILT-mat cells and ATL16T(-) cells, although they were ATL cells, showed rather low surface ICAM-1 expression and ICAM-1 mRNA expression. Southern blot hybridization showed that only two and four bands were found in ILT-mat and ATL16T(-) cells, respectively, whereas > 10 bands were detected in other ATL cells. These results suggest that monoclonal integration of HTLV-1 provirus to the genome of T cell, especially the number of integration sites, is one of the factors for induction of ICAM-1 molecules. "
],
"offsets": [
[
0,
1231
]
]
}
] | [
{
"id": "9219058_T1",
"type": "Protein",
"text": [
"intercellular adhesion molecule-1"
],
"offsets": [
[
34,
67
]
],
"normalized": []
},
{
"id": "9219058_T2",
"type": "Protein",
"text": [
"intercellular adhesion molecule-1"
],
"offsets": [
[
197,
230
]
],
"normalized": []
},
{
"id": "9219058_T3",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
232,
238
]
],
"normalized": []
},
{
"id": "9219058_T4",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
397,
403
]
],
"normalized": []
},
{
"id": "9219058_T5",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
473,
479
]
],
"normalized": []
},
{
"id": "9219058_T6",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
626,
632
]
],
"normalized": []
},
{
"id": "9219058_T7",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
816,
822
]
],
"normalized": []
},
{
"id": "9219058_T8",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
838,
844
]
],
"normalized": []
},
{
"id": "9219058_T9",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
1213,
1219
]
],
"normalized": []
}
] | [
{
"id": "9219058_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
20,
30
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_T1"
}
]
},
{
"id": "9219058_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
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[
176,
186
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_T3"
}
]
},
{
"id": "9219058_E3",
"type": "Regulation",
"trigger": {
"text": [
"influence"
],
"offsets": [
[
370,
379
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_E4"
}
]
},
{
"id": "9219058_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
384,
393
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_T4"
}
]
},
{
"id": "9219058_E5",
"type": "Transcription",
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"text": [
"expression"
],
"offsets": [
[
453,
463
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_T5"
}
]
},
{
"id": "9219058_E6",
"type": "Transcription",
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"text": [
"expression"
],
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638,
648
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_T6"
}
]
},
{
"id": "9219058_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
823,
833
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_T7"
}
]
},
{
"id": "9219058_E8",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
850,
860
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_T8"
}
]
},
{
"id": "9219058_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1200,
1209
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9219058_T9"
}
]
}
] | [
{
"id": "9219058_1",
"entity_ids": [
"9219058_T2",
"9219058_T3"
]
}
] | [] |
9185506 | 9185506 | [
{
"id": "9185506__text",
"type": "abstract",
"text": [
"Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras. \nGiant cell arteritis (GCA) is a vasculitic syndrome that preferentially affects medium and large-sized arteries. Glucocorticoid therapy resolves clinical symptoms within hours to days, but therapy has to be continued over several years to prevent disease relapses. It is not known whether and how glucocorticoids affect the function of the inflammatory infiltrate or why the disease persists subclinically despite chronic treatment. GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo. Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of IL-2, IL-1beta, and IL-6 mRNA, and by the diminished expression of inducible NO synthase. In contrast, synthesis of IFN-gamma mRNA was only slightly decreased, and expression of TGF-beta1 was unaffected. These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB in the xenotransplanted tissue. Dose-response experiments suggested that steroid doses currently used in clinical medicine are suboptimal in repressing NFkappaB-mediated cytokine production in the inflammatory lesions. Chronic steroid therapy was able to deplete the T cell products IL-2 and IFN-gamma, whereas the activation of tissue-infiltrating macrophages was only partially affected. IL-1beta transcription was abrogated; in contrast, TGF-beta1 mRNA synthesis was steroid resistant. The persistence of TGF-beta1-transcribing macrophages, despite paralysis of T cell function, may provide an explanation for the chronicity of the disease, and may identify a novel therapeutic target in this inflammatory vasculopathy. "
],
"offsets": [
[
0,
1961
]
]
}
] | [
{
"id": "9185506_T1",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
913,
917
]
],
"normalized": []
},
{
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}
] | [] | [] |
8761381 | 8761381 | [
{
"id": "8761381__text",
"type": "abstract",
"text": [
"Transcriptional analysis of Epstein-Barr virus gene expression in EBV-positive gastric carcinoma: unique viral latency in the tumour cells. \nAlthough case-oriented evidence for an association of Epstein-Barr virus (EBV) with gastric carcinoma has been accumulating recently, the interaction(s) between EBV and gastric epithelial cells is/are largely unknown. In this study, we examined seven EBV-positive gastric carcinoma tissues for viral gene expression at the mRNA level, from which studies on the EBV oncogenicity in human epithelial cells will benefit. Reverse transcription-PCR analysis showed that all seven EBV-positive tumour tissues constitutively expressed EBV nuclear antigen (EBNA) 1 mRNA, but not EBNA2 mRNA. The EBNA transcription was initiated from one of three EBNA promoters, Qp: by contrast, both Cp and Wp were silent, thus resulting in the lack of EBNA2 mRNA. Latent membrane protein (LMP) 2A mRNA was detected in three of seven cases; however, neither LMP1 nor LMP2B mRNA was detected in any of the tumours tested. Transcripts from the BamHI-A region of the viral genome were detectable in all cases. BZLF1 mRNA and the product, an immediate-early gene for EBV replication, was not expressed in any of them, thereby suggesting that the tumour cells carried EBV genomes in a tightly latent form. These findings further extended our previous data regarding EBV latency in gastric carcinoma cells at the protein level, and have affirmed that the programme of viral gene expression in the tumour more closely resembles 'latency I' represented by Burkitt's lymphoma than 'latency II' represented by the majority of nasopharyngeal carcinomas. "
],
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[
0,
1660
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{
"id": "8761381_T2",
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"EBNA2"
],
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712,
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]
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},
{
"id": "8761381_T3",
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870,
875
]
],
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"id": "8761381_T4",
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"id": "8761381_T5",
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],
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1124,
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}
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"ref_id": "8761381_T3"
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}
] | [] | [] |
8652841 | 8652841 | [
{
"id": "8652841__text",
"type": "abstract",
"text": [
"BCL-6 expression during B-cell activation. \nTranslocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma. Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner. The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA. Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12-myristate 13-acetate plus ionomycin, or CD40 ligand led to a five-fold to 35-fold decrease in BCL-6 mRNA levels. Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti-IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 MRNA expression, activated B cells from human germinal centers expressed BCL-6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34-fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms. These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression. "
],
"offsets": [
[
0,
1606
]
]
}
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0,
5
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73,
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172,
177
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782,
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"id": "8652841_T10",
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"id": "8652841_T11",
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"arguments": [
{
"role": "Theme",
"ref_id": "8652841_T16"
}
]
}
] | [] | [] |
9743506 | 9743506 | [
{
"id": "9743506__text",
"type": "abstract",
"text": [
"Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells [see comments] \nBACKGROUND: Platelet/endothelium interaction plays an important role in the pathophysiology of inflammation and atherosclerosis. The role of platelets for monocyte chemotactic protein-1 (MCP-1) secretion and surface expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells has been assessed. METHODS AND RESULTS: Monolayers of human umbilical vein endothelial cells were incubated with nonstimulated or ADP-activated platelets for 6 hours, and secretion of MCP-1 and surface expression of ICAM-1 were determined by ELISA and flow cytometry, respectively. In the presence of ADP-activated platelets, both MCP-1 secretion and ICAM-1 surface expression were significantly increased compared with nonstimulated platelets (P<0.02). Activation of the transcription factor nuclear factor-kappaB (NF-kappaB) determined by electrophoretic mobility shift assay and kappaB-dependent transcriptional activity was enhanced in the presence of activated platelets. In addition, ADP-activated platelets induced MCP-1 and ICAM-1 promoter-dependent transcription. Liposomal transfection of a double-stranded kappaB phosphorothioate oligonucleotide, but not of the mutated form, inhibited MCP-1 secretion and surface expression of ICAM-1 on activated endothelium (P<0.05). CONCLUSIONS: The present study indicates that activated platelets modulate chemotactic (MCP-1) and adhesive (ICAM-1) properties of endothelial cells via an NF-kappaB-dependent mechanism. Platelet-induced activation of the NF-kappaB system might contribute to early inflammatory events in atherogenesis. "
],
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]
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"role": "Theme",
"ref_id": "9743506_E17"
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]
},
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]
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},
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],
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]
]
},
"arguments": [
{
"role": "Theme",
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}
]
}
] | [
{
"id": "9743506_1",
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]
},
{
"id": "9743506_2",
"entity_ids": [
"9743506_T3",
"9743506_T4"
]
}
] | [] |
7998962 | 7998962 | [
{
"id": "7998962__text",
"type": "abstract",
"text": [
"Constitutive nuclear NF-kappa B in cells of the monocyte lineage. \nIn monocytes, the nuclear factor NF-kappa B has been invoked as an important transcription factor in the expression of cytokine genes, of cell-surface receptors and in the expression of human immunodeficiency virus. In such cells, DNA binding activity of NF-kappa B can be detected without intentional stimulation. In our studies, cells of the human monocytic line Mono Mac 6, cultured in medium containing fetal-calf serum and low levels of lipopolysaccharide (LPS), also exhibit such 'constitutive' NF-kappa B, as demonstrated by mobility-shift analysis of nuclear extracts. This nuclear NF-kappa B was still present when contaminant LPS was removed by ultrafiltration and when serum was omitted. Protein-DNA complexes of constitutive NF-kappa B are similar in mobility to the LPS-induced NF-kappa B and both are recognized by an antibody specific to the p50 subunit of NF-kappa B. By contrast, treatment of cells with pyrrolidine dithiocarbamate (PDTC) will only block LPS-induced NF-kappa B, but not the constitutive binding protein. Using LPS-free and serum-free conditions, constitutive NF-kappa B can be detected in different cell lines of the monocytic lineage (HL60, U937, THP-1, Mono Mac 1 and Mono Mac 6), but not in Molt 4 T cells or K562 stem cells. When ordered according to stage of maturation, the amount of constitutive NF-kappa B was not increased in more mature cell lines. Furthermore, when inducing differentiation in Mono Mac 6 cells, with vitamin D3, no change in constitutive or inducible NF-kappa B can be detected. Analysis of primary cells revealed substantial constitutive NF-kappa B-binding activity in blood monocytes, pleural macrophages and alveolar macrophages. The constitutive NF-kappa B appears to be functionally active, since a low level of tumour necrosis factor (TNF) transcript is detectable in monocytes, and this level can be increased by blocking transcript degradation using cycloheximide. The level of constitutive NF-kappa B in these cells is variable and is frequently found to be lower in the more mature macrophages. Constitutive NF-kappa B was not maintained by autocrine action of cytokines TNF, interleukin 6, interleukin 10, granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor, since neutralizing antibodies did not reduce constitutive DNA-binding activity. Furthermore, blockade of prostaglandin or leukotriene biosynthesis did not affect constitutive NF-kappa B. (ABSTRACT TRUNCATED AT 400 WORDS) "
],
"offsets": [
[
0,
2557
]
]
}
] | [
{
"id": "7998962_T1",
"type": "Protein",
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"p50 subunit"
],
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924,
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],
"normalized": []
},
{
"id": "7998962_T2",
"type": "Protein",
"text": [
"interleukin 6"
],
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2215,
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]
],
"normalized": []
},
{
"id": "7998962_T3",
"type": "Protein",
"text": [
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],
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],
"normalized": []
},
{
"id": "7998962_T4",
"type": "Protein",
"text": [
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],
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],
"normalized": []
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"id": "7998962_T5",
"type": "Protein",
"text": [
"macrophage colony-stimulating factor"
],
"offsets": [
[
2298,
2334
]
],
"normalized": []
}
] | [] | [] | [] |
8804437 | 8804437 | [
{
"id": "8804437__text",
"type": "abstract",
"text": [
"Attenuated function of a variant form of the helix-loop-helix protein, Id-3, generated by an alternative splicing mechanism. \nThe Id family of helix-loop-helix proteins function as negative regulators of DNA binding, basic helix-loop-helix proteins in the regulation of cell growth and differentiation. We report here on the identification of a 17 kDa variant of the 14 kDa Id-3 protein termed Id-3L (long version) which possesses a unique 60 amino acid carboxy-terminus generated by read through of a 'coding intron' and alternative splicing. Northern analysis revealed expression of a minor 1.1 kb Id-3L transcript together with the predominant 0.95 kb Id-3 transcript in the majority of adult human tissues analysed. The variant Id-3L protein is functionally distinguishable from conventional Id-3 since in in vitro DNA mobility shift assays, it was greatly impaired in its ability to abrogate binding of the basic helix-loop-helix protein, E47, to an E box recognition sequence. "
],
"offsets": [
[
0,
983
]
]
}
] | [
{
"id": "8804437_T1",
"type": "Protein",
"text": [
"Id-3"
],
"offsets": [
[
71,
75
]
],
"normalized": []
},
{
"id": "8804437_T2",
"type": "Protein",
"text": [
"Id-3"
],
"offsets": [
[
374,
378
]
],
"normalized": []
},
{
"id": "8804437_T3",
"type": "Protein",
"text": [
"Id-3"
],
"offsets": [
[
655,
659
]
],
"normalized": []
},
{
"id": "8804437_T4",
"type": "Protein",
"text": [
"Id-3"
],
"offsets": [
[
796,
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]
],
"normalized": []
},
{
"id": "8804437_T5",
"type": "Protein",
"text": [
"E47"
],
"offsets": [
[
944,
947
]
],
"normalized": []
}
] | [
{
"id": "8804437_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"Attenuated function"
],
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[
0,
19
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8804437_T1"
}
]
},
{
"id": "8804437_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"generated by"
],
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77,
89
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8804437_T1"
}
]
},
{
"id": "8804437_E3",
"type": "Transcription",
"trigger": {
"text": [
"read through"
],
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484,
496
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8804437_T2"
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]
},
{
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"expression"
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]
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"arguments": [
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"role": "Theme",
"ref_id": "8804437_T3"
}
]
},
{
"id": "8804437_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"abrogate"
],
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888,
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]
]
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"arguments": [
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"role": "Theme",
"ref_id": "8804437_E6"
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]
},
{
"id": "8804437_E6",
"type": "Binding",
"trigger": {
"text": [
"binding"
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"offsets": [
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904
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8804437_T5"
}
]
}
] | [] | [] |
10029589 | 10029589 | [
{
"id": "10029589__text",
"type": "abstract",
"text": [
"The Megakaryocyte/Platelet-specific enhancer of the alpha2beta1 integrin gene: two tandem AP1 sites and the mitogen-activated protein kinase signaling cascade. \nThe alpha2beta1 integrin, a collagen receptor on platelets and megakaryocytes, is required for normal platelet function. Transcriptional regulation of the alpha2 integrin gene in cells undergoing megakaryocytic differentiation requires a core promoter between bp -30 and -92, a silencer between bp -92 and -351, and megakaryocytic enhancers in the distal 5' flank. We have now identified a 229-bp region of the distal 5' flank of the alpha2 integrin gene required for high-level enhancer activity in cells with megakaryocytic features. Two tandem AP1 binding sites with dyad symmetry are required for enhancer activity and for DNA-protein complex formation with members of the c-fos/c-jun family. The requirement for AP1 activation suggested a role for the mitogen-activated protein kinase (MAPK) signaling pathway in regulating alpha2 integrin gene expression. Inhibition of the MAP kinase cascade with PD98059, a specific inhibitor of MAPK kinase 1, prevented the expression of the alpha2 integrin subunit in cells induced to become megakaryocytic. We provide a model of megakaryocytic differentiation in which expression of the alpha2 integrin gene requires signaling via the MAP kinase pathway to activate two tandem AP1 binding sites in the alpha2 integrin enhancer. "
],
"offsets": [
[
0,
1433
]
]
}
] | [
{
"id": "10029589_T1",
"type": "Protein",
"text": [
"alpha2 integrin"
],
"offsets": [
[
316,
331
]
],
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},
{
"id": "10029589_T2",
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"alpha2 integrin"
],
"offsets": [
[
595,
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]
],
"normalized": []
},
{
"id": "10029589_T3",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
838,
843
]
],
"normalized": []
},
{
"id": "10029589_T4",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
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844,
849
]
],
"normalized": []
},
{
"id": "10029589_T5",
"type": "Protein",
"text": [
"alpha2 integrin"
],
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990,
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]
],
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{
"id": "10029589_T6",
"type": "Protein",
"text": [
"MAPK kinase 1"
],
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},
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"id": "10029589_T7",
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"alpha2 integrin"
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},
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"id": "10029589_T8",
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"text": [
"alpha2 integrin"
],
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[
1407,
1422
]
],
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}
] | [
{
"id": "10029589_E1",
"type": "Regulation",
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"text": [
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]
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"ref_id": "10029589_T1"
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},
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"id": "10029589_E2",
"type": "Positive_regulation",
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"text": [
"requires"
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]
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"role": "Theme",
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] | [] | [] |
7935451 | 7935451 | [
{
"id": "7935451__text",
"type": "abstract",
"text": [
"Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA (p65)-mediated induction of the c-rel gene. \nThe tax gene product of human T-cell leukemia virus type I (HTLV-I) is a potent transcriptional activator that both stimulates viral gene expression and activates an array of cellular genes involved in T-cell growth. Tax acts indirectly by inducing or modifying the action of various host transcription factors, including members of the NF-kappa B/Rel family of enhancer-binding proteins. In resting T cells, many of these NF-kappa B/Rel factors are sequestered in the cytoplasm by various ankyrin-rich inhibitory proteins, including I kappa B alpha. HTLV-I Tax expression leads to the constitutive nuclear expression of biologically active NF-kappa B and c-Rel complexes; however, the biochemical mechanism(s) underlying this response remains poorly understood. In this study, we demonstrate that Tax-stimulated nuclear expression of NF-kappa B in both HTLV-I-infected and Tax-transfected human T cells is associated with the phosphorylation and rapid proteolytic degradation of I kappa B alpha. In contrast to prior in vitro studies, at least a fraction of the phosphorylated form of I kappa B alpha remains physically associated with the NF-kappa B complex in vivo but is subject to rapid degradation, thereby promoting the nuclear translocation of the active NF-kappa B complex. We further demonstrate that Tax induction of nuclear c-Rel expression is activated by the RelA (p65) subunit of NF-kappa B, which activates transcription of the c-rel gene through an intrinsic kappa B enhancer element. In normal cells, the subsequent accumulation of nuclear c-Rel acts to inhibit its own continued production, indicating the presence of an autoregulatory loop. (ABSTRACT TRUNCATED AT 250 WORDS) "
],
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0,
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{
"id": "7935451_2",
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}
] | [] |
9053449 | 9053449 | [
{
"id": "9053449__text",
"type": "abstract",
"text": [
"Involvement of Egr-1/RelA synergy in distinguishing T cell activation from tumor necrosis factor-alpha-induced NF-kappa B1 transcription. \nNF-kappa B is an important transcription factor required for T cell proliferation and other immunological functions. The NF-kappa B1 gene encodes a 105-kD protein that is the precursor of the p50 component of NF-kappa B. Previously, we and others have demonstrated that NF-kappa B regulates the NF-kappa B1 gene. In this manuscript we have investigated the molecular mechanisms by which T cell lines stimulated with phorbol 12-myristate 13-acetate (PMA) and phytohemagglutin (PHA) display significantly higher levels of NF-kappa B1 encoding transcripts than cells stimulated with tumor necrosis factor-alpha, despite the fact that both stimuli activate NF-kappa B. Characterization of the NF-kappa B1 promoter identified an Egr-1 site which was found to be essential for both the PMA/PHA-mediated induction as well as the synergistic activation observed after the expression of the RelA subunit of NF-kappa B and Egr-1. Furthermore, Egr-1 induction was required for endogenous NF-kappa B1 gene expression, since PMA/PHA-stimulated T cell lines expressing antisense Egr-1 RNA were inhibited in their ability to upregulate NF-kappa B1 transcription. Our studies indicate that transcriptional synergy mediated by activation of both Egr-1 and NF-kappa B may have important ramifications in T cell development by upregulating NF-kappa B1 gene expression. "
],
"offsets": [
[
0,
1489
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}
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{
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}
] | [] |
2122173 | 2122173 | [
{
"id": "2122173__text",
"type": "abstract",
"text": [
"Interferon-gamma and the sexual dimorphism of autoimmunity. \nThe sexual difference in the incidence of autoimmune diseases has remained an enigma for many years. In the examination of the induction of autoimmunity in transgenic mice, evidence has been obtained further implicating the lymphokine interferon-gamma in the etiology of autoimmunity. Sex steroid regulation of the production of this molecule, as well as other cytokines, may help explain the gender-specific differences in the immune system, including autoimmunity. "
],
"offsets": [
[
0,
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]
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"id": "2122173_T2",
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],
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]
],
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}
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"trigger": {
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "2122173_T2"
}
]
}
] | [] | [] |
9261367 | 9261367 | [
{
"id": "9261367__text",
"type": "abstract",
"text": [
"Inhibition of human immunodeficiency virus type 1 replication in vitro by a novel combination of anti-Tat single-chain intrabodies and NF-kappa B antagonists. \nHuman immunodeficiency virus type 1 (HIV-1) Tat, an early regulatory protein that is critical for viral gene expression and replication, transactivates the HIV-1 long terminal repeat (LTR) via its binding to the transactivation response element (TAR) and, along with other cellular factors, increases viral transcription initiation and elongation. Tat also superactivates the HIV-1 promoter through a TAR-independent mechanism, including tumor necrosis factor alpha-induced and protein kinase C (PKC)-dependent activation of NF-kappa B, and inhibitors of Tat and NF-kappa B cooperatively down-regulate this Tat-mediated LTR superactivation. In this study, a combined pharmacologic and genetic strategy using two PKC (NF-kappa B) inhibitors, pentoxifylline (PTX) and Go-6976, and a stably expressed anti-Tat single-chain intracellular antibody (sFv intrabody) was employed to obtain cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. Treatment of cells with PTX and Go-6976 resulted in cooperative inhibition of both HIV-1 LTR-driven gene expression and HIV-1 replication. In addition, the combined use of anti-Tat sFv intrabodies and the two NF-kappa B inhibitors retained the virus in the latent state for as long as 45 days. The combined treatment resulted in more durable inhibition of HIV-1 replication than was seen with the NF-kappa B inhibitors alone or the anti-Tat sFv intrabodies alone. Together, these results suggest that in future clinical gene therapy trials, a combined pharmacologic and genetic strategy like the one reported here may improve the survival of transduced cells and prolong clinical benefit. "
],
"offsets": [
[
0,
1818
]
]
}
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"id": "9261367_T1",
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],
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],
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204,
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]
],
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},
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"id": "9261367_T3",
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],
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},
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"id": "9261367_T4",
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"id": "9261367_T5",
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1566,
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{
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"type": "Binding",
"trigger": {
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357,
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"arguments": [
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"role": "Theme",
"ref_id": "9261367_T2"
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] | [] | [] |
9209284 | 9209284 | [
{
"id": "9209284__text",
"type": "abstract",
"text": [
"AP-1 derived from mature monocytes and astrocytes preferentially interacts with the HTLV-I promoter central 21 bp repeat. \nCharacterization of the cellular transcription factors interacting with the human T cell lymphotropic virus type I (HTLV-I) long terminal repeat (LTR) is essential to dissecting the mechanisms involved in viral transcription that may be pertinent to the oncogenic and neuropathogenic processes associated with HTLV-I infection in both the immune and nervous systems. Electrophoretic mobility shift (EMS) analyses utilizing oligonucleotides homologous to each of the 21 bp repeat elements reacted with nuclear extracts derived from cell lines of lymphocytic, monocytic, neuronal, and glial cell origin have demonstrated differential binding of cellular factors to the three 21 bp repeats (1-4). ATF/CREB and Sp family members interacted with the 21 bp repeats to form DNA-protein complexes common to all cell types examined. However, a unique DNA-protein complex was detected when the promoter central 21 bp repeat was reacted with nuclear extracts derived from either the U-373 MG glioblastoma cell line or the THP-1 mature monocytic cell line. Based on nucleotide sequence requirements and immunoreactivity, we demonstrate that this DNA-protein complex is comprised of the AP-1 components, Fos and Jun. "
],
"offsets": [
[
0,
1327
]
]
}
] | [] | [] | [] | [] |
1313226 | 1313226 | [
{
"id": "1313226__text",
"type": "abstract",
"text": [
"Leukotriene B4 stimulates c-fos and c-jun gene transcription and AP-1 binding activity in human monocytes. \nWe have examined the effect of leukotriene B4 (LTB4), a potent lipid proinflammatory mediator, on the expression of the proto-oncogenes c-jun and c-fos. In addition, we looked at the modulation of nuclear factors binding specifically to the AP-1 element after LTB4 stimulation. LTB4 increased the expression of the c-fos gene in a time- and concentration-dependent manner. The c-jun mRNA, which is constitutively expressed in human peripheral-blood monocytes at relatively high levels, was also slightly augmented by LTB4, although to a much lower extent than c-fos. The kinetics of expression of the two genes were also slightly different, with c-fos mRNA reaching a peak at 15 min after stimulation and c-jun at 30 min. Both messages rapidly declined thereafter. Stability of the c-fos and c-jun mRNA was not affected by LTB4, as assessed after actinomycin D treatment. Nuclear transcription studies in vitro showed that LTB4 increased the transcription of the c-fos gene 7-fold and the c-jun gene 1.4-fold. Resting monocytes contained nuclear factors binding to the AP-1 element, but stimulation of monocytes with LTB4 induced greater AP-1-binding activity of nuclear proteins. These results indicate that LTB4 may regulate the production of different cytokines by modulating the yield and/or the function of transcription factors such as AP-1-binding proto-oncogene products. "
],
"offsets": [
[
0,
1488
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]
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244,
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1097,
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15,
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"ref_id": "1313226_E15"
}
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"declined"
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852,
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"role": "Theme",
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"declined"
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"affected"
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"role": "Theme",
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}
] | [] | [] |
2407588 | 2407588 | [
{
"id": "2407588__text",
"type": "abstract",
"text": [
"Octamer transcription factors and the cell type-specificity of immunoglobulin gene expression. \nAntibodies are produced exclusively in B lymphocytes. The expression of the antibody-encoding genes, the immunoglobulin (Ig) genes, is also restricted to B cells. The octamer sequence ATGCAAAT is present in the promoter and the enhancer of Ig genes, and plays an important role in its tissue-specific expression. This sequence motif is a binding site for nuclear proteins, the so-called octamer transcription factors (Oct or OTF factors). The Oct-1 protein is present in all cell types analyzed so far, whereas Oct-2A and Oct-2B are found mainly in B lymphocytes. All three proteins show the same sequence specificity and binding affinity. It appears that the B cell-specific expression of Ig genes is mediated at least in part by cell type-specific Oct factors, and that there are both quantitative and qualitative differences between Oct-1 and Oct-2 factors. Recently, a number of other octamer factor variants were identified. Many of these may be created by alternative splicing of a primary transcript of one Oct factor gene and may serve a specific function in the fine tuning of gene expression. "
],
"offsets": [
[
0,
1199
]
]
}
] | [
{
"id": "2407588_T1",
"type": "Protein",
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"Oct-1"
],
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]
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"normalized": []
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"id": "2407588_T2",
"type": "Protein",
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"Oct-2A"
],
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]
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"id": "2407588_T3",
"type": "Protein",
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],
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618,
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]
],
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{
"id": "2407588_T4",
"type": "Protein",
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],
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]
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},
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"id": "2407588_T5",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
942,
947
]
],
"normalized": []
}
] | [
{
"id": "2407588_E1",
"type": "Gene_expression",
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"text": [
"present"
],
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"role": "Theme",
"ref_id": "2407588_T1"
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"type": "Gene_expression",
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"found"
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"role": "Theme",
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"type": "Gene_expression",
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"arguments": [
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"role": "Theme",
"ref_id": "2407588_T2"
}
]
}
] | [] | [] |
8605348 | 8605348 | [
{
"id": "8605348__text",
"type": "abstract",
"text": [
"Coexpression of the interleukin-13 and interleukin-4 genes correlates with their physical linkage in the cytokine gene cluster on human chromosome 5q23-31. \nInterleukin-13 (IL-13) and IL-4 are cytokines produced by T cells that are encoded by the q23-31 region of human chromosome 5. To investigate the regulation of IL-13 gene expression by T cells, we isolated and sequenced the human IL-13 gene, analyzed its 5'-flanking region for potential transcriptional activation elements, and examined its expression in nontransformed T-lineage cell populations. The human IL-13 gene was located 12.5-kb upstream of the IL-4 gene and 2-kb downstream of a CpG island. The IL-13 gene 5' flank region included a segment with sequence homology to P elements of the IL-4 promoter involved in transcriptional activation in T cells. Mutation of the IL-13 P element site significantly reduced IL-13 promoter activity in response to T-cell activation. Oligonucleotides containing the IL-13 or IL-4 P element sites specifically bound the transcriptional activator protein, nuclear factor-activated T cells, preformed (NF-ATp), when incubated with nuclear protein extracts from activated T cells. Similar to IL-4, IL-13 mRNA expression was highest in T-cell populations enriched for cells that had previously been primed in vivo or in vitro, indicating that priming increases the expression of the IL-13 and IL-4 genes in a coordinate manner. Because the primed T cells contain higher levels of nuclear NF-ATp, capable of binding to P elements of the IL-4 and IL-13 promoters, than do freshly-isolated T cells, the NF-AT-binding P elements are attractive candidates to mediate the coordinate expression of these two cytokine genes. "
],
"offsets": [
[
0,
1714
]
]
}
] | [
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"id": "8605348_T1",
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],
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20,
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]
],
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},
{
"id": "8605348_T2",
"type": "Protein",
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"interleukin-4"
],
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39,
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]
],
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},
{
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],
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]
],
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},
{
"id": "8605348_T4",
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],
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173,
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]
],
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},
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"id": "8605348_T5",
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],
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]
],
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],
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]
],
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},
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],
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]
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],
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],
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],
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]
],
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],
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],
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]
],
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},
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],
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]
],
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],
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]
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},
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],
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]
],
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],
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]
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],
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1542,
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]
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"id": "8605348_T30",
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],
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},
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884,
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]
],
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},
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"id": "8605348_T36",
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],
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]
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"P elements"
],
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],
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}
] | [
{
"id": "8605348_E1",
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0,
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]
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"role": "Theme",
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0,
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]
]
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"role": "Theme",
"ref_id": "8605348_T1"
}
]
},
{
"id": "8605348_E3",
"type": "Binding",
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"text": [
"linkage"
],
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]
]
},
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"role": "Theme",
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},
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"role": "Theme",
"ref_id": "8605348_T2"
}
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"produced"
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]
]
},
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{
"role": "Theme",
"ref_id": "8605348_T5"
}
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"text": [
"produced"
],
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203,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8605348_T4"
}
]
},
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"id": "8605348_E6",
"type": "Regulation",
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"text": [
"regulation"
],
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]
]
},
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"role": "Theme",
"ref_id": "8605348_E7"
}
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"expression"
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]
]
},
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"role": "Theme",
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]
},
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"role": "Theme",
"ref_id": "8605348_T7"
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]
},
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"id": "8605348_E9",
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"involved"
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]
]
},
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"role": "Theme",
"ref_id": "8605348_E10"
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"role": "CSite",
"ref_id": "8605348_T30"
}
]
},
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"id": "8605348_E10",
"type": "Positive_regulation",
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"text": [
"transcriptional activation"
],
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]
]
},
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"role": "Theme",
"ref_id": "8605348_T11"
}
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"id": "8605348_E11",
"type": "Negative_regulation",
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"text": [
"reduced"
],
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]
]
},
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"role": "Theme",
"ref_id": "8605348_E12"
}
]
},
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"id": "8605348_E12",
"type": "Regulation",
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"text": [
"in response to"
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]
},
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"role": "Theme",
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"higher levels"
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"binding"
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"role": "Theme",
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"ref_id": "8605348_T43"
}
]
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"text": [
"mediate"
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"arguments": [
{
"role": "Theme",
"ref_id": "8605348_E26"
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"type": "Positive_regulation",
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"text": [
"mediate"
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"arguments": [
{
"role": "Theme",
"ref_id": "8605348_T22"
}
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}
] | [
{
"id": "8605348_1",
"entity_ids": [
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] | [] |
8668213 | 8668213 | [
{
"id": "8668213__text",
"type": "abstract",
"text": [
"Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes. \nTranscription factors of the NFAT family play a key role in the transcription of cytokine genes and other genes during the immune response. We have identified two new isoforms of the transcription factor NFAT1 (previously termed NFATp) that are the predominant isoforms expressed in murine and human T cells. When expressed in Jurkat T cells, recombinant NFAT1 is regulated, as expected, by the calmodulin-dependent phosphatase calcineurin, and its function is inhibited by the immunosuppressive agent cyclosporin A (CsA). Transactivation by recombinant NFAT1 in Jurkat T cells requires dual stimulation with ionomycin and phorbol 12-myristate 13-acetate; this activity is potentiated by coexpression of constitutively active calcineurin and is inhibited by CsA. Immunocytochemical analysis indicates that recombinant NFAT1 localizes in the cytoplasm of transiently transfected T cells and translocates into the nucleus in a CsA-sensitive manner following ionomycin stimulation. When expressed in COS cells, however, NFAT1 is capable of transactivation, but it is not regulated correctly: its subcellular localization and transcriptional function are not affected by stimulation of the COS cells with ionomycin and phorbol 12-myristate 13-acetate. Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response. "
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] | [] |
9817603 | 9817603 | [
{
"id": "9817603__text",
"type": "abstract",
"text": [
"Transcriptional regulation of the beta-casein gene by cytokines: cross-talk between STAT5 and other signaling molecules. \nThe beta-casein promoter has been widely used to monitor the activation of STAT (signal transducer and activator of transcription)5 since STAT5 was originally found as a mediator of PRL-inducible beta-casein expression. However, not only is expression of the beta-casein gene regulated by STAT5 but it is also affected by other molecules such as glucocorticoid and Ras. In this report, we describe the transcriptional regulation of the beta-casein gene by cytokines in T cells. We have found that the beta-casein gene is expressed in a cytotoxic T cell line, CTLL-2, in response to interleukin-2 (IL-2), which activates STAT5. While IL-4 does not activate STAT5, it induces expression of STAT5-regulated genes in CTLL-2, i.e. beta-casein, a cytokine-inducible SH2-containing protein (CIS), and oncostatin M (OSM), suggesting that STAT6 activated by IL-4 substitutes for the function of STAT5 in T cells. IL-2-induced beta-casein expression was enhanced by dexamethasone, and this synergistic effect of Dexamethasone requires the sequence between -155 and -193 in the beta-casein promoter. Coincidentally, a deletion of this region enhanced the IL-2-induced expression of beta-casein. Expression of an active form of Ras, Ras(G12V), suppressed the IL-2-induced beta-casein and OSM gene expression, and the negative effect of Ras is mediated by the region between -105 and -193 in the beta-casein promoter. In apparent contradiction, expression of a dominant negative form of Ras, RasN17, also inhibited IL-2-induced activation of the promoter containing the minimal beta-casein STAT5 element as well as the promoters of CIS and OSM. In addition, Ras(G12V) complemented signaling by an erythropoietin receptor mutant defective in Ras activation and augmented the activation of the beta-casein promoter by the mutant erythropoietin receptor signaling, suggesting a possible role of Ras in Stat5-mediated gene expression. These results collectively reveal a complex interaction of STAT5 with other signaling pathways and illustrate that regulation of gene expression requires integration of opposing signals. "
],
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[
0,
2227
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}
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}
]
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"inhibited"
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]
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1623
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"augmented"
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},
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"signaling"
],
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]
},
"arguments": [
{
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"ref_id": "9817603_T45"
}
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] | [
{
"id": "9817603_1",
"entity_ids": [
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"9817603_T20"
]
},
{
"id": "9817603_2",
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]
},
{
"id": "9817603_3",
"entity_ids": [
"9817603_T12",
"9817603_T13"
]
}
] | [] |
9634075 | 9634075 | [
{
"id": "9634075__text",
"type": "abstract",
"text": [
"Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells. \nTuberculosis has emerged as an epidemic, extended by the large number of individuals infected with human immunodeficiency virus type 1 (HIV-1). The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis (M. tuberculosis) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system. These experiments are of prime importance considering that CD4-expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals. Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR, it was first found that culture protein filtrates (CFP) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM. The implication of protein tyrosine kinase(s), protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM-mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7. It was also determined, using electrophoresis mobility shift assays, that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB. M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type, but not the kappaB-mutated, HIV-1 LTR region. Finally, the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha. The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection. "
],
"offsets": [
[
0,
1952
]
]
}
] | [
{
"id": "9634075_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
658,
661
]
],
"normalized": []
},
{
"id": "9634075_T2",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1773,
1782
]
],
"normalized": []
}
] | [
{
"id": "9634075_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expressing"
],
"offsets": [
[
662,
672
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9634075_T1"
}
]
}
] | [] | [] |
9974401 | 9974401 | [
{
"id": "9974401__text",
"type": "abstract",
"text": [
"Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet. \nBecause oleic acid is implicated in the antiatherogenic effects attributed to the Mediterranean diet, we investigated whether this fatty acid can modulate endothelial activation, ie, the concerted expression of gene products involved in leukocyte recruitment and early atherogenesis. We incubated sodium oleate with human umbilical vein endothelial cells for 0 to 72 hours, followed by coincubation of oleate with human recombinant tumor necrosis factor, interleukin (IL)-1alpha, IL-1beta, IL-4, Escherichia coli lipopolysaccharide (LPS), or phorbol 12-myristate 13-acetate for a further 6 to 24 hours. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 was monitored by cell surface enzyme immunoassays or flow cytometry, and steady-state levels of VCAM-1 mRNA were assessed by Northern blot analysis. At 10 to 100 micromol/L for >24 hours, oleate inhibited the expression of all adhesion molecules tested. After a 72-hour incubation with oleate and a further 16-hour incubation with oleate plus 1 microg/mL LPS, VCAM-1 expression was reduced by >40% compared with control. Adhesion of monocytoid U937 cells to LPS-treated endothelial cells was reduced concomitantly. Oleate also produced a quantitatively similar reduction of VCAM-1 mRNA levels on Northern blot analysis and inhibited nuclear factor-kappaB activation on electrophoretic mobility shift assays. Incubation of endothelial cells with oleate for 72 hours decreased the relative proportions of saturated (palmitic and stearic) acids in total cell lipids and increased the proportions of oleate in total cell lipids without significantly changing the relative proportions of polyunsaturated fatty acids. Although less potent than polyunsaturated fatty acids in inhibiting endothelial activation, oleic acid may contribute to the prevention of atherogenesis through selective displacement of saturated fatty acids in cell membrane phospholipids and a consequent modulation of gene expression for molecules involved in monocyte recruitment. "
],
"offsets": [
[
0,
2218
]
]
}
] | [
{
"id": "9974401_T1",
"type": "Protein",
"text": [
"interleukin (IL)-1alpha"
],
"offsets": [
[
599,
622
]
],
"normalized": []
},
{
"id": "9974401_T2",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
624,
632
]
],
"normalized": []
},
{
"id": "9974401_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
634,
638
]
],
"normalized": []
},
{
"id": "9974401_T4",
"type": "Protein",
"text": [
"vascular cell adhesion molecule-1"
],
"offsets": [
[
777,
810
]
],
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},
{
"id": "9974401_T5",
"type": "Protein",
"text": [
"VCAM-1"
],
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[
812,
818
]
],
"normalized": []
},
{
"id": "9974401_T6",
"type": "Protein",
"text": [
"E-selectin"
],
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821,
831
]
],
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},
{
"id": "9974401_T7",
"type": "Protein",
"text": [
"intercellular adhesion molecule-1"
],
"offsets": [
[
837,
870
]
],
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},
{
"id": "9974401_T8",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
967,
973
]
],
"normalized": []
},
{
"id": "9974401_T9",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
1231,
1237
]
],
"normalized": []
},
{
"id": "9974401_T10",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
1445,
1451
]
],
"normalized": []
}
] | [
{
"id": "9974401_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
763,
773
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_T6"
}
]
},
{
"id": "9974401_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
763,
773
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_T7"
}
]
},
{
"id": "9974401_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
763,
773
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_T5"
}
]
},
{
"id": "9974401_E4",
"type": "Transcription",
"trigger": {
"text": [
"levels"
],
"offsets": [
[
957,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_T8"
}
]
},
{
"id": "9974401_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1066,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_E9"
}
]
},
{
"id": "9974401_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1066,
1075
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_E8"
}
]
},
{
"id": "9974401_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1066,
1075
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_E10"
}
]
},
{
"id": "9974401_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
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1080,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "9974401_T5"
}
]
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"id": "9974401_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
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1080,
1090
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "9974401_T6"
}
]
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{
"id": "9974401_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
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1080,
1090
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_T7"
}
]
},
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"id": "9974401_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1238,
1248
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_T9"
}
]
},
{
"id": "9974401_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduced"
],
"offsets": [
[
1253,
1260
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_E11"
}
]
},
{
"id": "9974401_E13",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduction"
],
"offsets": [
[
1432,
1441
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9974401_T10"
}
]
}
] | [
{
"id": "9974401_1",
"entity_ids": [
"9974401_T4",
"9974401_T5"
]
}
] | [] |
7917514 | 7917514 | [
{
"id": "7917514__text",
"type": "abstract",
"text": [
"Role of HIV-1 Nef expression in activation pathways in CD4+ T cells. \nThe role of the human immunodeficiency virus (HIV-1) Nef protein in T cell activation pathways was investigated using a Jurkat CD4+ cell line stably transfected with a Nef expression vector. Secretion of IL-2 and TNF-alpha, surface expression of IL-2R, and DNA-binding activity of NF-kappa B and AP-1 (Fos/Jun) complex in response to phorbol myristate acetate, TNF-alpha, or immobilized antibodies to CD3 were monitored. These parameters were not modified by Nef expression in Jurkat cells, whereas stimulation with the same stimuli resulted in partial inhibition of LTR activation in Nef+ Jurkat cells. This inhibition was not mediated through Nef phosphorylation on Thr-15 or GTP-binding activity because mutations in critical sites did not alter this inhibition. Analysis of truncated LTRs confirmed that inhibition of LTR activation was not mediated through NF-kappa B-binding activity but through the region containing the negative responding elements (NREs). These results suggest that Nef downmodulates LTR activation without significantly inhibiting the capacity of T cells to respond to immunological activations. "
],
"offsets": [
[
0,
1193
]
]
}
] | [
{
"id": "7917514_T1",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
14,
17
]
],
"normalized": []
},
{
"id": "7917514_T2",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
55,
58
]
],
"normalized": []
},
{
"id": "7917514_T3",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
123,
126
]
],
"normalized": []
},
{
"id": "7917514_T4",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
197,
200
]
],
"normalized": []
},
{
"id": "7917514_T5",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
238,
241
]
],
"normalized": []
},
{
"id": "7917514_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
274,
278
]
],
"normalized": []
},
{
"id": "7917514_T7",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
283,
292
]
],
"normalized": []
},
{
"id": "7917514_T8",
"type": "Protein",
"text": [
"Fos"
],
"offsets": [
[
372,
375
]
],
"normalized": []
},
{
"id": "7917514_T9",
"type": "Protein",
"text": [
"Jun"
],
"offsets": [
[
376,
379
]
],
"normalized": []
},
{
"id": "7917514_T10",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
431,
440
]
],
"normalized": []
},
{
"id": "7917514_T11",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
529,
532
]
],
"normalized": []
},
{
"id": "7917514_T12",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
655,
658
]
],
"normalized": []
},
{
"id": "7917514_T13",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
715,
718
]
],
"normalized": []
},
{
"id": "7917514_T14",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
1062,
1065
]
],
"normalized": []
},
{
"id": "7917514_T24",
"type": "Entity",
"text": [
"Thr-15"
],
"offsets": [
[
738,
744
]
],
"normalized": []
}
] | [
{
"id": "7917514_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
18,
28
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T1"
}
]
},
{
"id": "7917514_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"transfected"
],
"offsets": [
[
219,
230
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E3"
}
]
},
{
"id": "7917514_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
242,
252
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T5"
}
]
},
{
"id": "7917514_E4",
"type": "Localization",
"trigger": {
"text": [
"Secretion"
],
"offsets": [
[
261,
270
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T6"
}
]
},
{
"id": "7917514_E5",
"type": "Localization",
"trigger": {
"text": [
"Secretion"
],
"offsets": [
[
261,
270
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T7"
}
]
},
{
"id": "7917514_E6",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
331,
347
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T9"
}
]
},
{
"id": "7917514_E7",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
331,
347
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T8"
}
]
},
{
"id": "7917514_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
392,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E5"
}
]
},
{
"id": "7917514_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
392,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E7"
}
]
},
{
"id": "7917514_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
392,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E4"
},
{
"role": "Cause",
"ref_id": "7917514_T10"
}
]
},
{
"id": "7917514_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
392,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E6"
},
{
"role": "Cause",
"ref_id": "7917514_T10"
}
]
},
{
"id": "7917514_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
392,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E7"
},
{
"role": "Cause",
"ref_id": "7917514_T10"
}
]
},
{
"id": "7917514_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
392,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E6"
}
]
},
{
"id": "7917514_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
392,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E5"
},
{
"role": "Cause",
"ref_id": "7917514_T10"
}
]
},
{
"id": "7917514_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"response"
],
"offsets": [
[
392,
400
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E4"
}
]
},
{
"id": "7917514_E16",
"type": "Regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
517,
525
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E4"
},
{
"role": "Cause",
"ref_id": "7917514_E20"
}
]
},
{
"id": "7917514_E17",
"type": "Regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
517,
525
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E6"
},
{
"role": "Cause",
"ref_id": "7917514_E20"
}
]
},
{
"id": "7917514_E18",
"type": "Regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
517,
525
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E5"
},
{
"role": "Cause",
"ref_id": "7917514_E20"
}
]
},
{
"id": "7917514_E19",
"type": "Regulation",
"trigger": {
"text": [
"modified"
],
"offsets": [
[
517,
525
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_E7"
},
{
"role": "Cause",
"ref_id": "7917514_E20"
}
]
},
{
"id": "7917514_E20",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
533,
543
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T11"
}
]
},
{
"id": "7917514_E21",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
719,
734
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T13"
},
{
"role": "Site",
"ref_id": "7917514_T24"
}
]
},
{
"id": "7917514_E22",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
[
752,
768
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7917514_T13"
}
]
}
] | [] | [] |
9177217 | 9177217 | [
{
"id": "9177217__text",
"type": "abstract",
"text": [
"Specific complex formation between the type II bare lymphocyte syndrome-associated transactivators CIITA and RFX5. \nTwo of the genes defective in the five complementation groups identified in the class II-negative bare lymphocyte syndrome or corresponding laboratory mutants have been cloned. One gene encodes a protein, RFX5, that is a member of the RFX family of DNA binding proteins. The other, CIITA, encodes a large protein with a defined acidic transcriptional activation domain; this protein does not interact with DNA. Expression plasmids encoding regions of RFX5 fused to the GAL4 DNA binding domain activated transcription from a reporter construct containing GAL4 sites in a cotransfection assay in the Raji human B cell line. However, these plasmids produced transcriptional activity in HeLa cells only in conjunction with interferon gamma stimulation, a condition in which expression of both CIITA and class II major histocompatibility complex surface proteins are induced. Furthermore, these plasmids were not active in RJ2.2.5, an in vitro mutagenized derivative of Raji in which both copies of CIITA are defective. Transcriptional activation by the RFX5 fusion protein could be restored in RJ2.2.5 by cotransfection with a CIITA expression plasmid. Finally, a direct interaction between RFX5 and CIITA was detected with the yeast two-hybrid and far-Western blot assays. Thus, RFX5 can activate transcription only in cooperation with CIITA. RFX5 and CIITA associate to form a complex capable of activating transcription from class II major histocompatibility complex promoters. In this complex, promoter specificity is determined by the DNA binding domain of RFX5 and the general transcription apparatus is recruited by the acidic activation domain of CIITA. "
],
"offsets": [
[
0,
1774
]
]
}
] | [
{
"id": "9177217_T1",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
99,
104
]
],
"normalized": []
},
{
"id": "9177217_T2",
"type": "Protein",
"text": [
"RFX5"
],
"offsets": [
[
109,
113
]
],
"normalized": []
},
{
"id": "9177217_T3",
"type": "Protein",
"text": [
"RFX5"
],
"offsets": [
[
321,
325
]
],
"normalized": []
},
{
"id": "9177217_T4",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
398,
403
]
],
"normalized": []
},
{
"id": "9177217_T5",
"type": "Protein",
"text": [
"RFX5"
],
"offsets": [
[
567,
571
]
],
"normalized": []
},
{
"id": "9177217_T6",
"type": "Protein",
"text": [
"GAL4"
],
"offsets": [
[
585,
589
]
],
"normalized": []
},
{
"id": "9177217_T7",
"type": "Protein",
"text": [
"GAL4"
],
"offsets": [
[
670,
674
]
],
"normalized": []
},
{
"id": "9177217_T8",
"type": "Protein",
"text": [
"interferon gamma"
],
"offsets": [
[
835,
851
]
],
"normalized": []
},
{
"id": "9177217_T9",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
905,
910
]
],
"normalized": []
},
{
"id": "9177217_T10",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
1110,
1115
]
],
"normalized": []
},
{
"id": "9177217_T11",
"type": "Protein",
"text": [
"RFX5"
],
"offsets": [
[
1165,
1169
]
],
"normalized": []
},
{
"id": "9177217_T12",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
1239,
1244
]
],
"normalized": []
},
{
"id": "9177217_T13",
"type": "Protein",
"text": [
"RFX5"
],
"offsets": [
[
1303,
1307
]
],
"normalized": []
},
{
"id": "9177217_T14",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
1312,
1317
]
],
"normalized": []
},
{
"id": "9177217_T15",
"type": "Protein",
"text": [
"RFX5"
],
"offsets": [
[
1392,
1396
]
],
"normalized": []
},
{
"id": "9177217_T16",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
1449,
1454
]
],
"normalized": []
},
{
"id": "9177217_T17",
"type": "Protein",
"text": [
"RFX5"
],
"offsets": [
[
1456,
1460
]
],
"normalized": []
},
{
"id": "9177217_T18",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
1465,
1470
]
],
"normalized": []
},
{
"id": "9177217_T19",
"type": "Protein",
"text": [
"RFX5"
],
"offsets": [
[
1674,
1678
]
],
"normalized": []
},
{
"id": "9177217_T20",
"type": "Protein",
"text": [
"CIITA"
],
"offsets": [
[
1767,
1772
]
],
"normalized": []
},
{
"id": "9177217_T32",
"type": "Entity",
"text": [
"DNA binding domain"
],
"offsets": [
[
1652,
1670
]
],
"normalized": []
}
] | [
{
"id": "9177217_E1",
"type": "Binding",
"trigger": {
"text": [
"complex formation"
],
"offsets": [
[
9,
26
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9177217_T1"
},
{
"role": "Theme",
"ref_id": "9177217_T2"
}
]
},
{
"id": "9177217_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"defective"
],
"offsets": [
[
133,
142
]
]
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] | [] | [] |
10383397 | 10383397 | [
{
"id": "10383397__text",
"type": "abstract",
"text": [
"3-deazaadenosine, a S-adenosylhomocysteine hydrolase inhibitor, has dual effects on NF-kappaB regulation. Inhibition of NF-kappaB transcriptional activity and promotion of IkappaBalpha degradation. \nPreviously we reported that 3-deazaadenosine (DZA), a potent inhibitor and substrate for S-adenosylhomocysteine hydrolase inhibits bacterial lipopolysaccharide-induced transcription of tumor necrosis factor-alpha and interleukin-1beta in mouse macrophage RAW 264.7 cells. In this study, we demonstrate the effects of DZA on nuclear factor-kappaB (NF-kappaB) regulation. DZA inhibits the transcriptional activity of NF-kappaB through the hindrance of p65 (Rel-A) phosphorylation without reduction of its nuclear translocation and DNA binding activity. The inhibitory effect of DZA on NF-kappaB transcriptional activity is potentiated by the addition of homocysteine. Taken together, DZA promotes the proteolytic degradation of IkappaBalpha, but not IkappaBbeta, resulting in an increase of DNA binding activity of NF-kappaB in the nucleus in the absence of its transcriptional activity in RAW 264.7 cells. The reduction of IkappaBalpha by DZA is neither involved in IkappaB kinase complex activation nor modulated by the addition of homocysteine. This study strongly suggests that DZA may be a potent drug for the treatment of diseases in which NF-kappaB plays a central pathogenic role, as well as a useful tool for studying the regulation and physiological functions of NF-kappaB. "
],
"offsets": [
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384,
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416,
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]
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],
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1121,
1133
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],
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}
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"id": "10383397_E3",
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"text": [
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185,
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]
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"id": "10383397_E9",
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"text": [
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],
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"ref_id": "10383397_E10"
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},
{
"id": "10383397_E10",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
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[
661,
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]
]
},
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"role": "Theme",
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}
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},
{
"id": "10383397_E11",
"type": "Positive_regulation",
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885,
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]
},
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},
{
"id": "10383397_E13",
"type": "Protein_catabolism",
"trigger": {
"text": [
"proteolytic degradation"
],
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"id": "10383397_E14",
"type": "Protein_catabolism",
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"proteolytic degradation"
],
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"ref_id": "10383397_T9"
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{
"id": "10383397_E15",
"type": "Negative_regulation",
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"text": [
"reduction"
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1108,
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"ref_id": "10383397_T10"
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},
{
"id": "10383397_E16",
"type": "Regulation",
"trigger": {
"text": [
"modulated"
],
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[
1202,
1211
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10383397_E15"
}
]
}
] | [
{
"id": "10383397_1",
"entity_ids": [
"10383397_T6",
"10383397_T7"
]
}
] | [] |
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Dataset Card for BioNLP 2009
The BioNLP Shared Task 2009 was organized by GENIA Project and its corpora were curated based on the annotations of the publicly available GENIA Event corpus and an unreleased (blind) section of the GENIA Event corpus annotations, used for evaluation.
Citation Information
@inproceedings{kim-etal-2009-overview,
title = "Overview of {B}io{NLP}{'}09 Shared Task on Event Extraction",
author = "Kim, Jin-Dong and
Ohta, Tomoko and
Pyysalo, Sampo and
Kano, Yoshinobu and
Tsujii, Jun{'}ichi",
booktitle = "Proceedings of the {B}io{NLP} 2009 Workshop Companion Volume for Shared Task",
month = jun,
year = "2009",
address = "Boulder, Colorado",
publisher = "Association for Computational Linguistics",
url = "https://aclanthology.org/W09-1401",
pages = "1--9",
}
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