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2 | PMID-1419903 | [
{
"id": "PMID-1419903__text",
"type": "abstract",
"text": [
"Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. \nThe present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells. The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression. This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h. Similar effects were obtained for the c-fos gene. Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure. c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid-induced c-jun transcription. The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid-induced cells. In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts. Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism. Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element. (ABSTRACT TRUNCATED AT 250 WORDS)\n"
],
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"id": "PMID-1419903_T1",
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"c-jun"
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{
"id": "PMID-1419903_T2",
"type": "Protein",
"text": [
"type 1"
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176
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{
"id": "PMID-1419903_T3",
"type": "Protein",
"text": [
"2A protein phosphatases"
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"id": "PMID-1419903_T4",
"type": "Protein",
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"c-jun"
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{
"id": "PMID-1419903_T5",
"type": "Protein",
"text": [
"Mac-1 cell surface antigen"
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"id": "PMID-1419903_T6",
"type": "Protein",
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"c-myc"
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"id": "PMID-1419903_T7",
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"c-jun"
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"id": "PMID-1419903_T8",
"type": "Protein",
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"c-fos"
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"id": "PMID-1419903_T9",
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"c-jun"
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"id": "PMID-1419903_T10",
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"c-jun"
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"id": "PMID-1419903_T13",
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"c-jun"
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"id": "PMID-1419903_T15",
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"c-jun"
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"type": "Protein",
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"c-jun"
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}
] | [] | [] | [] |
4 | PMID-10364157 | [
{
"id": "PMID-10364157__text",
"type": "abstract",
"text": [
"Direct interaction of hematopoietic transcription factors PU.1 and GATA-1: functional antagonism in erythroid cells. \nMalignant transformation usually inhibits terminal cell differentiation but the precise mechanisms involved are not understood. PU.1 is a hematopoietic-specific Ets family transcription factor that is required for development of some lymphoid and myeloid lineages. PU.1 can also act as an oncoprotein as activation of its expression in erythroid precursors by proviral insertion or transgenesis causes erythroleukemias in mice. Restoration of terminal differentiation in the mouse erythroleukemia (MEL) cells requires a decline in the level of PU.1, indicating that PU.1 can block erythroid differentiation. Here we investigate the mechanism by which PU.1 interferes with erythroid differentiation. We find that PU.1 interacts directly with GATA-1, a zinc finger transcription factor required for erythroid differentiation. Interaction between PU.1 and GATA-1 requires intact DNA-binding domains in both proteins. PU.1 represses GATA-1-mediated transcriptional activation. Both the DNA binding and transactivation domains of PU.1 are required for repression and both domains are also needed to block terminal differentiation in MEL cells. We also show that ectopic expression of PU.1 in Xenopus embryos is sufficient to block erythropoiesis during normal development. Furthermore, introduction of exogenous GATA-1 in both MEL cells and Xenopus embryos and explants relieves the block to erythroid differentiation imposed by PU.1. Our results indicate that the stoichiometry of directly interacting but opposing transcription factors may be a crucial determinant governing processes of normal differentiation and malignant transformation.\n"
],
"offsets": [
[
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"id": "PMID-10364157_T1",
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"PU.1"
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"id": "PMID-10364157_T2",
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"id": "PMID-10364157_T3",
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"id": "PMID-10364157_T4",
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"id": "PMID-10364157_T7",
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"id": "PMID-10364157_T8",
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"id": "PMID-10364157_T9",
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"id": "PMID-10364157_T11",
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"id": "PMID-10364157_T12",
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"id": "PMID-10364157_T13",
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"GATA-1"
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"id": "PMID-10364157_T14",
"type": "Protein",
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"PU.1"
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"id": "PMID-10364157_T15",
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"PU.1"
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"id": "PMID-10364157_T16",
"type": "Protein",
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"GATA-1"
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"id": "PMID-10364157_T17",
"type": "Protein",
"text": [
"PU.1"
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}
] | [] | [] | [] |
6 | PMID-9223506 | [
{
"id": "PMID-9223506__text",
"type": "abstract",
"text": [
"Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity. \nWhen transcriptionally active, the human immunodeficiency virus (HIV) promoter contains a nucleosome-free region encompassing both the promoter/enhancer region and a large region (255 nucleotides [nt]) downstream of the transcription start site. We have previously identified new binding sites for transcription factors downstream of the transcription start site (nt 465 to 720): three AP-1 sites (I, II, and III), an AP3-like motif (AP3-L), a downstream binding factor (DBF) site, and juxtaposed Sp1 sites. Here, we show that the DBF site is an interferon-responsive factor (IRF) binding site and that the AP3-L motif binds the T-cell-specific factor NF-AT. Mutations that abolish the binding of each factor to its cognate site are introduced in an infectious HIV-1 molecular clone to study their effect on HIV-1 transcription and replication. Individual mutation of the DBF or AP3-L site as well as the double mutation AP-1(III)/AP3-L did not affect HIV-1 replication compared to that of the wild-type virus. In contrast, proviruses carrying mutations in the Sp1 sites were totally defective in terms of replication. Virus production occurred with slightly delayed kinetics for viruses containing combined mutations in the AP-1(III), AP3-L, and DBF sites and in the AP3-L and DBF-sites, whereas viruses mutated in the AP-1(I,II,III) and AP3-L sites and in the AP-1(I,II,III), AP3-L, and DBF sites exhibited a severely defective replicative phenotype. No RNA-packaging defect could be measured for any of the mutant viruses as determined by quantification of their HIV genomic RNA. Measurement of the transcriptional activity of the HIV-1 promoter after transient transfection of the HIV-1 provirus DNA or of long terminal repeat-luciferase constructs showed a positive correlation between the transcriptional and the replication defects for most mutants.\n"
],
"offsets": [
[
0,
2009
]
]
}
] | [
{
"id": "PMID-9223506_T1",
"type": "Protein",
"text": [
"Sp1"
],
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[
649,
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]
],
"normalized": []
},
{
"id": "PMID-9223506_T2",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
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]
],
"normalized": []
}
] | [] | [] | [] |
9 | PMID-9299590 | [
{
"id": "PMID-9299590__text",
"type": "abstract",
"text": [
"The role of Rel/NF-kappa B proteins in viral oncogenesis and the regulation of viral transcription. \nRel/NF-kappa B is a ubiquitous transcription factor that consists of multiple polypeptide subunits, and is subject to complex regulatory mechanisms that involve protein-protein interactions, phosphorylation, ubiquitination, proteolytic degradation, and nucleocytoplasmic translocation. The sophisticated control of Rel/NF-kappa B activity is not surprising since this transcription factor is involved in a wide array of cellular responses to extracellular cues, associated with growth, development, apoptosis, and pathogen invasion. Thus, it is not unexpected that this versatile cellular homeostatic switch would be affected by a variety of viral pathogens, which have evolved mechanisms to utilize various aspects of Rel/NF-kappa B activity to facilitate their replication, cell survival and possibly evasion of immune responses. This review will cover the molecular mechanisms that are utilized by mammalian oncogenic viruses to affect the activity of Rel/NF-kappa B transcription factors and the role of Rel/NF-kappa B in the regulation of viral gene expression and replication.\n"
],
"offsets": [
[
0,
1184
]
]
}
] | [] | [] | [] | [] |
10 | PMID-9121455 | [
{
"id": "PMID-9121455__text",
"type": "abstract",
"text": [
"Control of NFATx1 nuclear translocation by a calcineurin-regulated inhibitory domain. \nThe nuclear factor of activated T cells (NFAT) regulates cytokine gene expression in T cells through cis-acting elements located in the promoters of several cytokine genes. NFATx1, which is preferentially expressed in the thymus and peripheral blood leukocytes, is one of four members of the NFAT family of transcription factors. We have performed domain analysis of NFATx1 by examining the effects of deletion mutations. We found that NFATx1 DNA binding activity and interaction with AP-1 polypeptides were dependent on its central Rel similarity region and that transcriptional activation was reduced by deletions of either its N-terminal domain or its C-terminal domain, suggesting the presence of intrinsic transcriptional activation motifs in both regions. We also identified a potent inhibitory sequence within its N-terminal domain. We show that the inactivation of the inhibition was dependent on the activity of calcineurin, a calcium-calmodulin-dependent phosphatase. We also show that calcineurin associated with the N-terminal domain of NFATx1 at multiple docking sites and caused a reduction of size, indicative of dephosphorylation, in NFATx1. We have mapped the inhibitory activity to less than 60 residues, containing motifs that are conserved in all NFAT proteins. Finally, we demonstrate that deletion in NFATx1 of the mapped 60 residues leads to its nuclear translocation independent of calcium signaling. Our results support the model proposing that the N-terminal domain confers calcium-signaling dependence on NFATx1 transactivation activity by regulating its intracellular localization through a protein module that associates with calcineurin and is a target of its phosphatase activity.\n"
],
"offsets": [
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"id": "PMID-9121455_T1",
"type": "Protein",
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"NFATx1"
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"id": "PMID-9121455_T2",
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] | [] | [] | [] |
13 | PMID-10358154 | [
{
"id": "PMID-10358154__text",
"type": "abstract",
"text": [
"New immunosuppressive drug PNU156804 blocks IL-2-dependent proliferation and NF-kappa B and AP-1 activation. \nWe had previously shown that the drug undecylprodigiosin (UP) blocks human lymphocyte proliferation in vitro. We have now investigated the mechanism of action of a new analogue of UP, PNU156804, which shows a more favorable activity profile than UP in mice. We demonstrate here that the biological effect of PNU156804 in vitro is indistinguishable from UP: PNU156804 blocks human T cell proliferation in mid-late G1, as determined by cell cycle analysis, expression of cyclins, and cyclin-dependent kinases and retinoblastoma phosphorylation. In addition, we show that PNU156804 does not block significantly the induction of either IL-2 or IL-2R alpha- and gamma-chains but inhibits IL-2-dependent T cell proliferation. We have investigated several molecular pathways that are known to be activated by IL-2 in T cells. We show that PNU156804 does not inhibit c-myc and bcl-2 mRNA induction. On the other hand, PNU156804 efficiently inhibits the activation of the NF-kappa B and AP-1 transcription factors. PNU156804 inhibition of NF-kappa B activation is due to the inhibition of the degradation of I kappa B-alpha and I kappa B-beta. PNU156804 action is restricted to some signaling pathways; it does not affect NF-kappa B activation by PMA in T cells but blocks that induced by CD40 cross-linking in B lymphocytes. We conclude that the prodigiosin family of immunosuppressants is a new family of molecules that show a novel target specificity clearly distinct from that of other immunosuppressive drugs such as cyclosporin A, FK506, and rapamycin.\n"
],
"offsets": [
[
0,
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"id": "PMID-10358154_T1",
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"id": "PMID-10358154_T2",
"type": "Protein",
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"IL-2"
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"id": "PMID-10358154_T3",
"type": "Protein",
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"text": [
"c-myc"
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"id": "PMID-10358154_T6",
"type": "Protein",
"text": [
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},
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"id": "PMID-10358154_T7",
"type": "Protein",
"text": [
"I kappa B-alpha"
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},
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"id": "PMID-10358154_T8",
"type": "Protein",
"text": [
"I kappa B-beta"
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},
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"id": "PMID-10358154_T9",
"type": "Protein",
"text": [
"CD40"
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}
] | [] | [] | [] |
14 | PMID-1618911 | [
{
"id": "PMID-1618911__text",
"type": "abstract",
"text": [
"Heterodimerization and transcriptional activation in vitro by NF-kappa B proteins. \nThe NF-kappa B family of transcription proteins represents multiple DNA binding, rel related polypeptides that contribute to regulation of genes involved in immune responsiveness and inflammation, as well as activation of the HIV long terminal repeat. In this study multiple NF-kappa B related polypeptides ranging from 85 to 45 kDa were examined for their capacity to interact with the PRDII regulatory element of interferon beta and were shown to possess distinct intrinsic DNA binding affinities for this NF-kappa B site and form multiple DNA binding homo- and heterodimer complexes in co-renaturation experiments. Furthermore, using DNA templates containing two copies of the PRDII domain linked to the rabbit beta globin gene, the purified polypeptides specifically stimulated NF-kappa B dependent transcription in an in vitro reconstitution assay as heterodimers but not as p50 homodimers. These experiments emphasize the role of NF-kappa B dimerization as a distinct level of transcriptional control that may permit functional diversification of a limited number of regulatory proteins.\n"
],
"offsets": [
[
0,
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]
]
}
] | [
{
"id": "PMID-1618911_T1",
"type": "Protein",
"text": [
"rel"
],
"offsets": [
[
165,
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]
],
"normalized": []
},
{
"id": "PMID-1618911_T2",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
964,
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]
],
"normalized": []
}
] | [] | [] | [] |
19 | PMID-9862666 | [
{
"id": "PMID-9862666__text",
"type": "abstract",
"text": [
"Nuclear factor of activated T cells and AP-1 are insufficient for IL-2 promoter activation: requirement for CD28 up-regulation of RE/AP. \nIL-2 gene transcription in T cells requires both TCR and costimulatory signals. IL-2 promoter activation in Jurkat T cells stimulated with superantigen presented by Raji B cells requires CD28 activation. The addition of rCTLA4Ig, which blocks CD28 binding to its ligand, to the cultures decreased IL-2 promoter activation by >80%. Interestingly, CTLA4Ig did not significantly inhibit the activation of either NF of activated T cells (NFAT) or AP-1 reporters. Therefore, activation of NFAT and AP-1 is insufficient for IL-2 promoter activation. In contrast, an RE/AP reporter was blocked by CTLA4Ig by >90%. Thus, the requirement for CD28 in IL-2 promoter activation appears to be due to RE/AP and not the NFAT or AP-1 sites. In addition, these data suggest that transcriptional activation of RE/AP is not mediated by NFAT, because activation of a NFAT reporter is not affected by the addition of CTLA4Ig.\n"
],
"offsets": [
[
0,
1043
]
]
}
] | [
{
"id": "PMID-9862666_T1",
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"IL-2"
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[
66,
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]
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},
{
"id": "PMID-9862666_T2",
"type": "Protein",
"text": [
"CD28"
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[
108,
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]
],
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},
{
"id": "PMID-9862666_T3",
"type": "Protein",
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"IL-2"
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138,
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]
],
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"id": "PMID-9862666_T4",
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"id": "PMID-9862666_T5",
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"text": [
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"id": "PMID-9862666_T6",
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"id": "PMID-9862666_T7",
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"id": "PMID-9862666_T8",
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"normalized": []
},
{
"id": "PMID-9862666_T9",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
771,
775
]
],
"normalized": []
},
{
"id": "PMID-9862666_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
779,
783
]
],
"normalized": []
}
] | [] | [] | [] |
22 | PMID-8929546 | [
{
"id": "PMID-8929546__text",
"type": "abstract",
"text": [
"Regulation of cytokine and cytokine receptor expression by glucocorticoids. \nGlucocorticoids (GCS) profoundly inhibit several aspects of T cell immunity largely through inhibition of cytokine expression at the transcriptional and posttranscriptional levels. GCS were also reported to act indirectly by inducing transforming growth factor-beta expression, which in turn blocks T cell immunity. In exerting their antiproliferative effects, GCS diffuse into target cells where they bind their cytoplasmic receptor, which in turn translocates to the nucleus where it inhibits transcription of cytokine genes through direct binding to the glucocorticoid response elements (GRE), which are located in the promoter region of cytokine genes or, alternatively, through antagonism of the action of transcription factors required for optimal transcriptional activation. In contrast to their inhibitory effects on cytokine expression, GCS up-regulate cytokine receptor expression that correlates with enhanced cytokine effects on target cells. In this review, we summarize the current state of knowledge of the mechanism of action of GCS, including the phenomenon of steroid-induced rebound, which ensues upon GCS withdrawal.\n"
],
"offsets": [
[
0,
1214
]
]
}
] | [
{
"id": "PMID-8929546_T1",
"type": "Protein",
"text": [
"transforming growth factor-beta"
],
"offsets": [
[
311,
342
]
],
"normalized": []
}
] | [] | [] | [] |
23 | PMID-10225377 | [
{
"id": "PMID-10225377__text",
"type": "abstract",
"text": [
"Activation of nuclear factor-kappaB by lipopolysaccharide in mononuclear leukocytes is prevented by inhibitors of cytosolic phospholipase A2. \nIn monocytes, lipopolysaccharide induces synthesis and activity of the 85-kDa cytosolic phospholipase A2. This enzyme releases arachidonic acid and lyso-phospholipids from membranes which are metabolized to eicosanoids and platelet-activating-factor. These lipid mediators increase activity of transcription factors and expression of cytokine genes indicating a function for cytosolic phospholipase A2 in signal transduction and inflammation. We have shown previously that trifluoromethylketone inhibitors of cytosolic phospholipase A2 suppressed interleukin-1beta protein and steady-state mRNA levels in human lipopolysaccharide-stimulated peripheral blood mononuclear leukocytes. In this study, the subcellular mechanisms were analyzed by which trifluoromethylketones interfere with gene expression. We found that they reduced the initial interleukin-1beta mRNA transcription rate through prevention of degradation of inhibitor-kappaB alpha. Consequently, cytosolic activation, nuclear translocation and DNA-binding of nuclear factor-kappaB were decreased. Trifluoromethylketones ameliorate chronic inflammation in vivo. Thus, this therapeutic potency may reside in retention of inactive nuclear factor-kappaB in the cytosol thereby abrogating interleukin-1beta gene transcription.\n"
],
"offsets": [
[
0,
1427
]
]
}
] | [
{
"id": "PMID-10225377_T1",
"type": "Protein",
"text": [
"interleukin-1beta"
],
"offsets": [
[
690,
707
]
],
"normalized": []
},
{
"id": "PMID-10225377_T2",
"type": "Protein",
"text": [
"interleukin-1beta"
],
"offsets": [
[
984,
1001
]
],
"normalized": []
},
{
"id": "PMID-10225377_T3",
"type": "Protein",
"text": [
"inhibitor-kappaB alpha"
],
"offsets": [
[
1063,
1085
]
],
"normalized": []
},
{
"id": "PMID-10225377_T4",
"type": "Protein",
"text": [
"interleukin-1beta"
],
"offsets": [
[
1389,
1406
]
],
"normalized": []
}
] | [] | [] | [] |
32 | PMID-9252117 | [
{
"id": "PMID-9252117__text",
"type": "abstract",
"text": [
"EBF and E47 collaborate to induce expression of the endogenous immunoglobulin surrogate light chain genes. \nEarly B cell factor (EBF) and E47 participate in the transcriptional control of early B lymphocyte differentiation. With the aim of identifying genetic targets for these transcription factors, we stably transfected cDNAs encoding EBF or a covalent homodimer of E47, individually or together, into immature hematopoietic Ba/F3 cells, which lack both factors. In combination, EBF and E47 induce efficient expression of the endogenous immunoglobulin surrogate light chain genes, lambda5 and VpreB, whereas other pre-B cell-specific genes remain silent. Multiple functionally important EBF and E47 binding sites were identified in the lambda5 promoter/enhancer region, indicating that lambda5 is a direct genetic target for these transcription factors. Taken together, these data suggest that EBF and E47 synergize to activate expression of a subset of genes that define an early stage of the B cell lineage.\n"
],
"offsets": [
[
0,
1013
]
]
}
] | [
{
"id": "PMID-9252117_T1",
"type": "Protein",
"text": [
"EBF"
],
"offsets": [
[
0,
3
]
],
"normalized": []
},
{
"id": "PMID-9252117_T2",
"type": "Protein",
"text": [
"E47"
],
"offsets": [
[
8,
11
]
],
"normalized": []
},
{
"id": "PMID-9252117_T3",
"type": "Protein",
"text": [
"Early B cell factor"
],
"offsets": [
[
108,
127
]
],
"normalized": []
},
{
"id": "PMID-9252117_T4",
"type": "Protein",
"text": [
"EBF"
],
"offsets": [
[
129,
132
]
],
"normalized": []
},
{
"id": "PMID-9252117_T5",
"type": "Protein",
"text": [
"E47"
],
"offsets": [
[
138,
141
]
],
"normalized": []
},
{
"id": "PMID-9252117_T6",
"type": "Protein",
"text": [
"EBF"
],
"offsets": [
[
338,
341
]
],
"normalized": []
},
{
"id": "PMID-9252117_T7",
"type": "Protein",
"text": [
"E47"
],
"offsets": [
[
369,
372
]
],
"normalized": []
},
{
"id": "PMID-9252117_T8",
"type": "Protein",
"text": [
"EBF"
],
"offsets": [
[
482,
485
]
],
"normalized": []
},
{
"id": "PMID-9252117_T9",
"type": "Protein",
"text": [
"E47"
],
"offsets": [
[
490,
493
]
],
"normalized": []
},
{
"id": "PMID-9252117_T10",
"type": "Protein",
"text": [
"lambda5"
],
"offsets": [
[
584,
591
]
],
"normalized": []
},
{
"id": "PMID-9252117_T11",
"type": "Protein",
"text": [
"VpreB"
],
"offsets": [
[
596,
601
]
],
"normalized": []
},
{
"id": "PMID-9252117_T12",
"type": "Protein",
"text": [
"EBF"
],
"offsets": [
[
690,
693
]
],
"normalized": []
},
{
"id": "PMID-9252117_T13",
"type": "Protein",
"text": [
"E47"
],
"offsets": [
[
698,
701
]
],
"normalized": []
},
{
"id": "PMID-9252117_T14",
"type": "Protein",
"text": [
"lambda5"
],
"offsets": [
[
739,
746
]
],
"normalized": []
},
{
"id": "PMID-9252117_T15",
"type": "Protein",
"text": [
"lambda5"
],
"offsets": [
[
789,
796
]
],
"normalized": []
},
{
"id": "PMID-9252117_T16",
"type": "Protein",
"text": [
"EBF"
],
"offsets": [
[
897,
900
]
],
"normalized": []
},
{
"id": "PMID-9252117_T17",
"type": "Protein",
"text": [
"E47"
],
"offsets": [
[
905,
908
]
],
"normalized": []
}
] | [] | [] | [] |
35 | PMID-8428966 | [
{
"id": "PMID-8428966__text",
"type": "abstract",
"text": [
"Characterization of the nuclear and cytoplasmic components of the lymphoid-specific nuclear factor of activated T cells (NF-AT) complex. \nThe lymphoid-specific transcription complex, NF-AT, is involved in early gene activation in T cells and is assembled from a pre-existing, T cell restricted cytoplasmic factor and an inducible ubiquitous nuclear component within 30 min after activation through the antigen receptor. Recent studies have implicated the family of AP1 factors as components of the murine NF-AT complex. Evidence is provided here that the nuclear component of human NF-AT contains the phorbol ester-inducible transcription factor AP1 (Jun/Fos). We further characterize which AP1 family members can assume this role. Antisera to Fos inhibits NF-AT DNA binding as does an oligonucleotide containing a binding site for AP1. Constitutive expression in vivo of Fos, and to a lesser extent Fra-1, eliminates the requirement for phorbol 12-myristate 13-acetate (PMA) stimulation, leaving NF-AT-directed transcription responsive to calcium ionophore alone. Overexpression of cJun or JunD, but not JunB, also eliminates the requirement for PMA, indicating that many but not all Jun- and Fos-related proteins functionally activate NF-AT-dependent transcription in the presence of the cytoplasmic component. NF-AT DNA binding can be reconstituted in vitro using semi-purified AP1 proteins mixed with cytosol from T lymphocytes. Fos proteins are not needed for this reconstitution, and although JunB is not functional, it can participate in the NF-AT DNA binding complex. Finally, we have partially purified the cytoplasmic component of NF-AT and show by elution and renaturation from SDS-polyacrylamide gel electrophoresis gels that it has a molecular mass between 94 and 116 kDa and may have multiple differentially modified forms.\n"
],
"offsets": [
[
0,
1838
]
]
}
] | [
{
"id": "PMID-8428966_T1",
"type": "Protein",
"text": [
"Fra-1"
],
"offsets": [
[
900,
905
]
],
"normalized": []
},
{
"id": "PMID-8428966_T2",
"type": "Protein",
"text": [
"cJun"
],
"offsets": [
[
1083,
1087
]
],
"normalized": []
},
{
"id": "PMID-8428966_T3",
"type": "Protein",
"text": [
"JunD"
],
"offsets": [
[
1091,
1095
]
],
"normalized": []
},
{
"id": "PMID-8428966_T4",
"type": "Protein",
"text": [
"JunB"
],
"offsets": [
[
1105,
1109
]
],
"normalized": []
},
{
"id": "PMID-8428966_T5",
"type": "Protein",
"text": [
"JunB"
],
"offsets": [
[
1499,
1503
]
],
"normalized": []
}
] | [] | [] | [] |
40 | PMID-7892566 | [
{
"id": "PMID-7892566__text",
"type": "abstract",
"text": [
"[Regulation of transcription of the interleukin-2 gene in B-lymphocytes] \nSince most B cell clones immortalized with EBV virus can be induced to produce interleukin-2, a typical T cell cytokine, we studied the role of different elements of the IL-2 promoter in such clones by transfection. It was found, in particular, that the element TCEd, which binds the transcription factor NF-kB, is very active in all three B clones tested. This element has no activity in T cells of the Jurkat line. The NFATd element, which binds the transcription factor NFAT-1 and is very active in T cells, is only weakly active in one B clone and not at all in another. Different elements thus contribute to IL-2 promoter activity in different cells.\n"
],
"offsets": [
[
0,
730
]
]
}
] | [
{
"id": "PMID-7892566_T1",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
36,
49
]
],
"normalized": []
},
{
"id": "PMID-7892566_T2",
"type": "Protein",
"text": [
"interleukin-2"
],
"offsets": [
[
153,
166
]
],
"normalized": []
},
{
"id": "PMID-7892566_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
244,
248
]
],
"normalized": []
},
{
"id": "PMID-7892566_T4",
"type": "Protein",
"text": [
"NFAT-1"
],
"offsets": [
[
547,
553
]
],
"normalized": []
},
{
"id": "PMID-7892566_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
687,
691
]
],
"normalized": []
}
] | [] | [] | [] |
42 | PMID-8977228 | [
{
"id": "PMID-8977228__text",
"type": "abstract",
"text": [
"The state of maturation of monocytes into macrophages determines the effects of IL-4 and IL-13 on HIV replication. \nThe molecular mechanisms of the effects of IL-4 and IL-13 on HIV infection in human monocytes as they matured into monocyte-derived macrophages over 7 days were investigated using HIV-1(BaL), and low passage clinical strains. IL-4 and IL-13 up-regulated the expression of both genomic and spliced HIV mRNA in monocytes cultured on Teflon, as determined by Northern analysis and p24 Ag assay. Using a nuclear run-on assay, IL-4 stimulation was shown to enhance transcription by two- to threefold. IL-4 stimulated nuclear factor-kappaB nuclear translocation and binding before enhancement of HIV RNA expression. Conversely, IL-4 and IL-13 markedly and significantly inhibited HIV replication at the transcriptional level in monocyte-derived macrophages, and this occurred whether these cytokines were added before or after HIV infection. The reversal from stimulation to inhibition occurred after 3 to 5 days of adherence to plastic. IL-4 had no significant effect on HIV reverse transcription. The effect of both cytokines on the monocyte maturation/differentiation (CD11b, CD13, and CD26) and other macrophage markers (CD14 and CD68) was examined. IL-4 enhanced CD11b, but inhibited CD26 expression and delayed CD13 loss. IL-13 had similar effects on CD11b and CD13, but no effect on CD26. Hence, these cytokines do not simply enhance monocyte differentiation, but have complex and slightly divergent effects that impact on HIV replication probably through cell signaling pathways and nuclear factor-kappaB translocation.\n"
],
"offsets": [
[
0,
1638
]
]
}
] | [
{
"id": "PMID-8977228_T1",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
80,
84
]
],
"normalized": []
},
{
"id": "PMID-8977228_T2",
"type": "Protein",
"text": [
"IL-13"
],
"offsets": [
[
89,
94
]
],
"normalized": []
},
{
"id": "PMID-8977228_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
159,
163
]
],
"normalized": []
},
{
"id": "PMID-8977228_T4",
"type": "Protein",
"text": [
"IL-13"
],
"offsets": [
[
168,
173
]
],
"normalized": []
},
{
"id": "PMID-8977228_T5",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
342,
346
]
],
"normalized": []
},
{
"id": "PMID-8977228_T6",
"type": "Protein",
"text": [
"IL-13"
],
"offsets": [
[
351,
356
]
],
"normalized": []
},
{
"id": "PMID-8977228_T7",
"type": "Protein",
"text": [
"p24 Ag"
],
"offsets": [
[
494,
500
]
],
"normalized": []
},
{
"id": "PMID-8977228_T8",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
538,
542
]
],
"normalized": []
},
{
"id": "PMID-8977228_T9",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
612,
616
]
],
"normalized": []
},
{
"id": "PMID-8977228_T10",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
738,
742
]
],
"normalized": []
},
{
"id": "PMID-8977228_T11",
"type": "Protein",
"text": [
"IL-13"
],
"offsets": [
[
747,
752
]
],
"normalized": []
},
{
"id": "PMID-8977228_T12",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1048,
1052
]
],
"normalized": []
},
{
"id": "PMID-8977228_T13",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
1182,
1187
]
],
"normalized": []
},
{
"id": "PMID-8977228_T14",
"type": "Protein",
"text": [
"CD13"
],
"offsets": [
[
1189,
1193
]
],
"normalized": []
},
{
"id": "PMID-8977228_T15",
"type": "Protein",
"text": [
"CD26"
],
"offsets": [
[
1199,
1203
]
],
"normalized": []
},
{
"id": "PMID-8977228_T16",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
1235,
1239
]
],
"normalized": []
},
{
"id": "PMID-8977228_T17",
"type": "Protein",
"text": [
"CD68"
],
"offsets": [
[
1244,
1248
]
],
"normalized": []
},
{
"id": "PMID-8977228_T18",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1264,
1268
]
],
"normalized": []
},
{
"id": "PMID-8977228_T19",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
1278,
1283
]
],
"normalized": []
},
{
"id": "PMID-8977228_T20",
"type": "Protein",
"text": [
"CD26"
],
"offsets": [
[
1299,
1303
]
],
"normalized": []
},
{
"id": "PMID-8977228_T21",
"type": "Protein",
"text": [
"CD13"
],
"offsets": [
[
1327,
1331
]
],
"normalized": []
},
{
"id": "PMID-8977228_T22",
"type": "Protein",
"text": [
"IL-13"
],
"offsets": [
[
1338,
1343
]
],
"normalized": []
},
{
"id": "PMID-8977228_T23",
"type": "Protein",
"text": [
"CD11b"
],
"offsets": [
[
1367,
1372
]
],
"normalized": []
},
{
"id": "PMID-8977228_T24",
"type": "Protein",
"text": [
"CD13"
],
"offsets": [
[
1377,
1381
]
],
"normalized": []
},
{
"id": "PMID-8977228_T25",
"type": "Protein",
"text": [
"CD26"
],
"offsets": [
[
1400,
1404
]
],
"normalized": []
}
] | [] | [] | [] |
49 | PMID-9317151 | [
{
"id": "PMID-9317151__text",
"type": "abstract",
"text": [
"Dual effects of LPS antibodies on cellular uptake of LPS and LPS-induced proinflammatory functions. \nHuman phagocytes recognize bacterial LPS (endotoxin) through membrane CD14 (mCD14), a proinflammatory LPS receptor. This study tested the hypothesis that anti-LPS Abs neutralize endotoxin by blocking cellular uptake through mCD14. Ab-associated changes in the uptake and cellular distribution of FITC-LPS were assessed by flow cytometry and laser scanning confocal microscopy in human CD14-transfected Chinese hamster ovary fibroblasts (CHO-CD14 cells) and human peripheral blood monocytes. LPS core- and O-side chain-specific mAbs inhibited mCD14-mediated LPS uptake by both cell types in the presence of serum. O-side chain-specific mAb concurrently enhanced complement-dependent LPS uptake by monocytes through complement receptor-1 (CR1) and uptake by CHO-CD14 cells involving another heat-labile serum factor(s) and cell-associated recognition molecule(s). Core-specific mAb inhibited mCD14-mediated uptake of homologous and heterologous LPS, while producing less concurrent enhancement of non-mCD14-mediated LPS uptake. The modulation by anti-LPS mAbs of mCD14-mediated LPS uptake was associated with inhibition of LPS-induced nuclear factor-kappaB (NF-kappaB) translocation and TNF-alpha secretion in CHO-CD14 cells and monocytes, respectively, while mAb enhancement of non-mCD14-mediated LPS uptake stimulated these activities. LPS-specific Abs thus mediate anti-inflammatory and proinflammatory functions, respectively, by preventing target cell uptake of LPS through mCD14 and augmenting uptake through CR1 or other cell receptors.\n"
],
"offsets": [
[
0,
1643
]
]
}
] | [
{
"id": "PMID-9317151_T1",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
171,
175
]
],
"normalized": []
},
{
"id": "PMID-9317151_T2",
"type": "Protein",
"text": [
"mCD14"
],
"offsets": [
[
177,
182
]
],
"normalized": []
},
{
"id": "PMID-9317151_T3",
"type": "Protein",
"text": [
"mCD14"
],
"offsets": [
[
325,
330
]
],
"normalized": []
},
{
"id": "PMID-9317151_T4",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
486,
490
]
],
"normalized": []
},
{
"id": "PMID-9317151_T5",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
542,
546
]
],
"normalized": []
},
{
"id": "PMID-9317151_T6",
"type": "Protein",
"text": [
"mCD14"
],
"offsets": [
[
643,
648
]
],
"normalized": []
},
{
"id": "PMID-9317151_T7",
"type": "Protein",
"text": [
"complement receptor-1"
],
"offsets": [
[
815,
836
]
],
"normalized": []
},
{
"id": "PMID-9317151_T8",
"type": "Protein",
"text": [
"CR1"
],
"offsets": [
[
838,
841
]
],
"normalized": []
},
{
"id": "PMID-9317151_T9",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
861,
865
]
],
"normalized": []
},
{
"id": "PMID-9317151_T10",
"type": "Protein",
"text": [
"mCD14"
],
"offsets": [
[
991,
996
]
],
"normalized": []
},
{
"id": "PMID-9317151_T11",
"type": "Protein",
"text": [
"mCD14"
],
"offsets": [
[
1100,
1105
]
],
"normalized": []
},
{
"id": "PMID-9317151_T12",
"type": "Protein",
"text": [
"mCD14"
],
"offsets": [
[
1162,
1167
]
],
"normalized": []
},
{
"id": "PMID-9317151_T13",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1286,
1295
]
],
"normalized": []
},
{
"id": "PMID-9317151_T14",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
1313,
1317
]
],
"normalized": []
},
{
"id": "PMID-9317151_T15",
"type": "Protein",
"text": [
"mCD14"
],
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[
1382,
1387
]
],
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"id": "PMID-9317151_T16",
"type": "Protein",
"text": [
"mCD14"
],
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"normalized": []
},
{
"id": "PMID-9317151_T17",
"type": "Protein",
"text": [
"CR1"
],
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[
1614,
1617
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"normalized": []
}
] | [] | [] | [] |
50 | PMID-9712026 | [
{
"id": "PMID-9712026__text",
"type": "abstract",
"text": [
"A CD28-associated signaling pathway leading to cytokine gene transcription and T cell proliferation without TCR engagement. \nStimulation of resting human T cells with the CD28-specific mAb BW 828 induces proliferation and cytokine synthesis without further requirement for TCR coengagement. This observation prompted us to postulate that signal 2 (costimulatory signal) alone without signal 1 (TCR signal) can activate T cells. To test whether this putative function of CD28 is mediated via a particular signaling pathway, we compared early signaling events initiated in resting T cells by the stimulatory mAb BW 828 with signals triggered by the nonstimulating CD28 mAb 9.3. Stimulation of T cells with BW 828 induced an increase in intracellular Ca2+, but did not lead to detectable activation of the protein kinases p56(lck) and c-Raf-1. This pathway resulted in the induction of the transcription factors NF-kappa B, NF-AT, and proteins binding to the CD28 response element of the IL-2 promoter. On the other hand, stimulation of T cells with mAb 9.3 increased the level of intracellular Ca2+ and triggered the activation of p56(lck) and c-Raf-1, but was unable to induce the binding of transcription factors to the IL-2 promoter. In contrast to the differential signaling of BW 828 and 9.3 in resting T cells, the two mAbs exhibited a similar pattern of early signaling events in activated T cells and Jurkat cells (p56(lck) activation, association of phosphatidylinositol 3-kinase with CD28), indicating that the signaling capacity of CD28 changes with activation. These data support the view that stimulation through CD28 can induce some effector functions in T cells and suggest that this capacity is associated with a particular pattern of early signaling events.\n"
],
"offsets": [
[
0,
1773
]
]
}
] | [
{
"id": "PMID-9712026_T1",
"type": "Protein",
"text": [
"CD28"
],
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[
2,
6
]
],
"normalized": []
},
{
"id": "PMID-9712026_T2",
"type": "Protein",
"text": [
"CD28"
],
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[
171,
175
]
],
"normalized": []
},
{
"id": "PMID-9712026_T3",
"type": "Protein",
"text": [
"CD28"
],
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[
470,
474
]
],
"normalized": []
},
{
"id": "PMID-9712026_T4",
"type": "Protein",
"text": [
"CD28"
],
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662,
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]
],
"normalized": []
},
{
"id": "PMID-9712026_T5",
"type": "Protein",
"text": [
"p56(lck)"
],
"offsets": [
[
819,
827
]
],
"normalized": []
},
{
"id": "PMID-9712026_T6",
"type": "Protein",
"text": [
"c-Raf-1"
],
"offsets": [
[
832,
839
]
],
"normalized": []
},
{
"id": "PMID-9712026_T7",
"type": "Protein",
"text": [
"CD28"
],
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[
956,
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]
],
"normalized": []
},
{
"id": "PMID-9712026_T8",
"type": "Protein",
"text": [
"IL-2"
],
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985,
989
]
],
"normalized": []
},
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"id": "PMID-9712026_T9",
"type": "Protein",
"text": [
"p56(lck)"
],
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1129,
1137
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],
"normalized": []
},
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"id": "PMID-9712026_T10",
"type": "Protein",
"text": [
"c-Raf-1"
],
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[
1142,
1149
]
],
"normalized": []
},
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"id": "PMID-9712026_T11",
"type": "Protein",
"text": [
"IL-2"
],
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[
1220,
1224
]
],
"normalized": []
},
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"id": "PMID-9712026_T12",
"type": "Protein",
"text": [
"BW 828"
],
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[
1280,
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]
],
"normalized": []
},
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"id": "PMID-9712026_T13",
"type": "Protein",
"text": [
"9.3"
],
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[
1291,
1294
]
],
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},
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"id": "PMID-9712026_T14",
"type": "Protein",
"text": [
"p56(lck)"
],
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1421,
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],
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},
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"id": "PMID-9712026_T15",
"type": "Protein",
"text": [
"CD28"
],
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1492,
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],
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},
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"id": "PMID-9712026_T16",
"type": "Protein",
"text": [
"CD28"
],
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],
"normalized": []
},
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"id": "PMID-9712026_T17",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
1624,
1628
]
],
"normalized": []
}
] | [] | [] | [] |
51 | PMID-8158122 | [
{
"id": "PMID-8158122__text",
"type": "abstract",
"text": [
"Activation of nuclear factor kappa B in human neuroblastoma cell lines. \nThe nuclear factor kappa B (NF-kappa B) is a eukaryotic transcription factor. In B cells and macrophages it is constitutively present in cell nuclei, whereas in many other cell types, NF-kappa B translocates from cytosol to nucleus as a result of transduction by tumor necrosis factor alpha (TNF alpha), phorbol ester, and other polyclonal signals. Using neuroblastoma cell lines as models, we have shown that in neural cells NF-kappa B was present in the cytosol and translocated into nuclei as a result of TNF alpha treatment. The TNF alpha-activated NF-kappa B was transcriptionally functional. NF-kappa B activation by TNF alpha was not correlated with cell differentiation or proliferation. However, reagents such as nerve growth factor (NGF) and the phorbol ester phorbol 12-myristate 13-acetate (PMA), which induce phenotypical differentiation of the SH-SY5Y neuroblastoma cell line, activated NF-kappa B, but only in that particular cell line. In a NGF-responsive rat pheochromocytoma cell line, PC12, PMA activated NF-kappa B, whereas NGF did not. In other neuroblastoma cell lines, such as SK-N-Be(2), the lack of PMA induction of differentiation was correlated with the lack of NF-kappa B activation. We found, moreover, that in SK-N-Be(2) cells protein kinase C (PKC) enzymatic activity was much lower compared with that in a control cell line and that the low PKC enzymatic activity was due to low PKC protein expression. NF-kappa B was not activated by retinoic acid, which induced morphological differentiation of all the neuroblastoma cell lines used in the present study. Thus, NF-kappa B activation was not required for neuroblastoma cell differentiation. Furthermore, the results obtained with TNF alpha proved that NF-kappa B activation was not sufficient for induction of neuroblastoma differentiation.\n"
],
"offsets": [
[
0,
1897
]
]
}
] | [
{
"id": "PMID-8158122_T1",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
336,
363
]
],
"normalized": []
},
{
"id": "PMID-8158122_T2",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
365,
374
]
],
"normalized": []
},
{
"id": "PMID-8158122_T3",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
581,
590
]
],
"normalized": []
},
{
"id": "PMID-8158122_T4",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
606,
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]
],
"normalized": []
},
{
"id": "PMID-8158122_T5",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
696,
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]
],
"normalized": []
},
{
"id": "PMID-8158122_T6",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
1786,
1795
]
],
"normalized": []
}
] | [] | [] | [] |
53 | PMID-8663022 | [
{
"id": "PMID-8663022__text",
"type": "abstract",
"text": [
"Octamer binding factors and their coactivator can activate the murine PU.1 (spi-1) promoter. \nPU.1 (spi-1), a member of the Ets transcription factor family, is predominantly expressed in myeloid and B cells, activates many B cell and myeloid genes, and is critical for development of both of these lineages. Our previous studies (Chen, H.M., Ray-Gallet, D., Zhang, P., Hetherington, C.J., Gonzalez, D.A., Zhang, D.-E., Moreau-Gachelin, F., and Tenen, D.G.(1995) Oncogene 11, 1549-1560) demonstrate that the PU.1 promoter directs cell type-specific reporter gene expression in myeloid cell lines, and that PU.1 activates its own promoter in an autoregulatory loop. Here we show that the murine PU.1 promoter is also specifically and highly functional in B cell lines as well. Oct-1 and Oct-2 can bind specifically to a site at base pair -55 in vitro, and this site is specifically protected in B cells in vivo. We also demonstrate that two other sites contribute to promoter activity in B cells; an Sp1 binding site adjacent to the octamer site, and the PU.1 autoregulatory site. Finally, we show that the B cell coactivator OBF-1/Bob1/OCA-B is only expressed in B cells and not in myeloid cells, and that OBF-1/Bob1/OCA-B can transactivate the PU.1 promoter in HeLa and myeloid cells. This B cell restricted coactivator may be responsible for the B cell specific expression of PU.1 mediated by the octamer site.\n"
],
"offsets": [
[
0,
1412
]
]
}
] | [
{
"id": "PMID-8663022_T1",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
70,
74
]
],
"normalized": []
},
{
"id": "PMID-8663022_T2",
"type": "Protein",
"text": [
"spi-1"
],
"offsets": [
[
76,
81
]
],
"normalized": []
},
{
"id": "PMID-8663022_T3",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
94,
98
]
],
"normalized": []
},
{
"id": "PMID-8663022_T4",
"type": "Protein",
"text": [
"spi-1"
],
"offsets": [
[
100,
105
]
],
"normalized": []
},
{
"id": "PMID-8663022_T5",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
507,
511
]
],
"normalized": []
},
{
"id": "PMID-8663022_T6",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
605,
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]
],
"normalized": []
},
{
"id": "PMID-8663022_T7",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
693,
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]
],
"normalized": []
},
{
"id": "PMID-8663022_T8",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
775,
780
]
],
"normalized": []
},
{
"id": "PMID-8663022_T9",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
785,
790
]
],
"normalized": []
},
{
"id": "PMID-8663022_T10",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
998,
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]
],
"normalized": []
},
{
"id": "PMID-8663022_T11",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1053,
1057
]
],
"normalized": []
},
{
"id": "PMID-8663022_T12",
"type": "Protein",
"text": [
"OBF-1"
],
"offsets": [
[
1124,
1129
]
],
"normalized": []
},
{
"id": "PMID-8663022_T13",
"type": "Protein",
"text": [
"Bob1"
],
"offsets": [
[
1130,
1134
]
],
"normalized": []
},
{
"id": "PMID-8663022_T14",
"type": "Protein",
"text": [
"OCA-B"
],
"offsets": [
[
1135,
1140
]
],
"normalized": []
},
{
"id": "PMID-8663022_T15",
"type": "Protein",
"text": [
"OBF-1"
],
"offsets": [
[
1205,
1210
]
],
"normalized": []
},
{
"id": "PMID-8663022_T16",
"type": "Protein",
"text": [
"Bob1"
],
"offsets": [
[
1211,
1215
]
],
"normalized": []
},
{
"id": "PMID-8663022_T17",
"type": "Protein",
"text": [
"OCA-B"
],
"offsets": [
[
1216,
1221
]
],
"normalized": []
},
{
"id": "PMID-8663022_T18",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1244,
1248
]
],
"normalized": []
},
{
"id": "PMID-8663022_T19",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1377,
1381
]
],
"normalized": []
}
] | [] | [] | [] |
63 | PMID-9136080 | [
{
"id": "PMID-9136080__text",
"type": "abstract",
"text": [
"Structure and function analysis of the human myeloid cell nuclear differentiation antigen promoter: evidence for the role of Sp1 and not of c-Myb or PU.1 in myelomonocytic lineage-specific expression. \nThe human myeloid nuclear differentiation antigen (MNDA) is expressed specifically in maturing cells of the myelomonocytic lineage and in monocytes and granulocytes. Epitope enhancement was used to confirm the strict lineage- and stage-specific expression of MNDA in bone marrow as well as in other paraffin-embedded fixed tissues. A 1-kb region of the gene that includes 5' flanking sequence was reported earlier to contain functional promoter activity and was specifically demethylated in expressing cells in contrast to null cells. Further analysis has revealed that this 1-kb fragment promotes higher reporter gene activity in MNDA-expressing cells than non-expressing cells, indicating cell-specific differences in transactivation. This sequence contains consensus elements consistent with myeloid-specific gene expression, including a PU.1 consensus site near the major transcription start site and a cluster of c-Myb sites located several hundred bases upstream of this region. However, analysis of deletion mutants localized nearly all of the promoter activity to a short region (-73 to -16) that did not include the cluster of c-Myb sites. A 4-bp mutation of the core Sp1 consensus element (GC box) (-20) reduced overall promoter activity of the 1-kb fragment. Mutation of the PU.1 site did not significantly affect promoter activity. Only a small region (-35 to +22) including the Sp1 element and transcription start site, but not the PU.1 site was footprinted. The 4-bp mutation of the core Sp1 consensus element abolished footprinting at the site and an antibody super-shift reaction showed that Sp1 is one of the factors binding the consensus site. The Sp1 site also co-localizes with a DNase I hypersensitive site. The results indicate that DNA methylation, chromatin structure, and transactivation at an Sp1 site contribute to the highly restricted expression of this myelomonocytic lineage specific gene.\n"
],
"offsets": [
[
0,
2123
]
]
}
] | [
{
"id": "PMID-9136080_T1",
"type": "Protein",
"text": [
"myeloid cell nuclear differentiation antigen"
],
"offsets": [
[
45,
89
]
],
"normalized": []
},
{
"id": "PMID-9136080_T2",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
125,
128
]
],
"normalized": []
},
{
"id": "PMID-9136080_T3",
"type": "Protein",
"text": [
"c-Myb"
],
"offsets": [
[
140,
145
]
],
"normalized": []
},
{
"id": "PMID-9136080_T4",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
149,
153
]
],
"normalized": []
},
{
"id": "PMID-9136080_T5",
"type": "Protein",
"text": [
"myeloid nuclear differentiation antigen"
],
"offsets": [
[
212,
251
]
],
"normalized": []
},
{
"id": "PMID-9136080_T6",
"type": "Protein",
"text": [
"MNDA"
],
"offsets": [
[
253,
257
]
],
"normalized": []
},
{
"id": "PMID-9136080_T7",
"type": "Protein",
"text": [
"MNDA"
],
"offsets": [
[
461,
465
]
],
"normalized": []
},
{
"id": "PMID-9136080_T8",
"type": "Protein",
"text": [
"MNDA"
],
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[
833,
837
]
],
"normalized": []
},
{
"id": "PMID-9136080_T9",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1043,
1047
]
],
"normalized": []
},
{
"id": "PMID-9136080_T10",
"type": "Protein",
"text": [
"c-Myb"
],
"offsets": [
[
1120,
1125
]
],
"normalized": []
},
{
"id": "PMID-9136080_T11",
"type": "Protein",
"text": [
"c-Myb"
],
"offsets": [
[
1338,
1343
]
],
"normalized": []
},
{
"id": "PMID-9136080_T12",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1379,
1382
]
],
"normalized": []
},
{
"id": "PMID-9136080_T13",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1488,
1492
]
],
"normalized": []
},
{
"id": "PMID-9136080_T14",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1593,
1596
]
],
"normalized": []
},
{
"id": "PMID-9136080_T15",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1647,
1651
]
],
"normalized": []
},
{
"id": "PMID-9136080_T16",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1704,
1707
]
],
"normalized": []
},
{
"id": "PMID-9136080_T17",
"type": "Protein",
"text": [
"Sp1"
],
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[
1810,
1813
]
],
"normalized": []
},
{
"id": "PMID-9136080_T18",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1868,
1871
]
],
"normalized": []
},
{
"id": "PMID-9136080_T19",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
2021,
2024
]
],
"normalized": []
}
] | [] | [] | [] |
69 | PMID-9416887 | [
{
"id": "PMID-9416887__text",
"type": "abstract",
"text": [
"Cyclosporin A inhibits monocyte tissue factor activation in cardiac transplant recipients. \nBACKGROUND: Fibrin deposition and thrombosis have been implicated in both allograft rejection and vasculopathy after cardiac transplantation. Because monocytes play a pivotal role in the pathophysiology of intravascular coagulation activation through their ability to synthesize tissue factor (TF), we asked (1) whether monocyte TF activation occurs in cardiac transplant recipients and (2) whether monocyte TF expression is affected by treatment with cyclosporin A (CsA). METHODS AND RESULTS: We measured levels of TF activity in peripheral blood mononuclear cells and highly purified monocytes/macrophages from 10 consecutive cardiac transplant recipients and 10 healthy control subjects. TF activity generated by both unstimulated and endotoxin-stimulated cells was significantly higher in transplant recipients than in control subjects (P<.05). Increased monocyte TF expression in transplant recipients was shown to be adversely affected by treatment with CsA: TF induction was markedly reduced by CsA serum concentrations reaching peak CsA drug levels. Inhibition of TF induction in the presence of high CsA blood concentrations was also observed when stimulation of cells was performed with interferon-gamma or interleukin-1beta. As shown by reverse transcription-polymerase chain reaction and electrophoretic mobility shift assay, respectively, treatment with CsA leads to decreased TF mRNA expression and reduced activation of the NF-kappaB transcription factor, which is known to contribute to the induction of the TF promotor in human monocytes. CONCLUSIONS: This study demonstrates that TF activation, occurring in mononuclear cells of cardiac transplant recipients, is inhibited by treatment with CsA. Inhibition of monocyte TF induction by CsA may contribute to its successful use in cardiac transplant medicine and might be useful in managing further settings of vascular pathology also known to involve TF expression and NF-kappaB activation.\n"
],
"offsets": [
[
0,
2050
]
]
}
] | [
{
"id": "PMID-9416887_T1",
"type": "Protein",
"text": [
"tissue factor"
],
"offsets": [
[
32,
45
]
],
"normalized": []
},
{
"id": "PMID-9416887_T2",
"type": "Protein",
"text": [
"tissue factor"
],
"offsets": [
[
371,
384
]
],
"normalized": []
},
{
"id": "PMID-9416887_T3",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
386,
388
]
],
"normalized": []
},
{
"id": "PMID-9416887_T4",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
421,
423
]
],
"normalized": []
},
{
"id": "PMID-9416887_T5",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
500,
502
]
],
"normalized": []
},
{
"id": "PMID-9416887_T6",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
608,
610
]
],
"normalized": []
},
{
"id": "PMID-9416887_T7",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
783,
785
]
],
"normalized": []
},
{
"id": "PMID-9416887_T8",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
960,
962
]
],
"normalized": []
},
{
"id": "PMID-9416887_T9",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1057,
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]
],
"normalized": []
},
{
"id": "PMID-9416887_T10",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1164,
1166
]
],
"normalized": []
},
{
"id": "PMID-9416887_T11",
"type": "Protein",
"text": [
"interferon-gamma"
],
"offsets": [
[
1289,
1305
]
],
"normalized": []
},
{
"id": "PMID-9416887_T12",
"type": "Protein",
"text": [
"interleukin-1beta"
],
"offsets": [
[
1309,
1326
]
],
"normalized": []
},
{
"id": "PMID-9416887_T13",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1482,
1484
]
],
"normalized": []
},
{
"id": "PMID-9416887_T14",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1616,
1618
]
],
"normalized": []
},
{
"id": "PMID-9416887_T15",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1690,
1692
]
],
"normalized": []
},
{
"id": "PMID-9416887_T16",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1829,
1831
]
],
"normalized": []
},
{
"id": "PMID-9416887_T17",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
2010,
2012
]
],
"normalized": []
}
] | [] | [] | [] |
71 | PMID-9018153 | [
{
"id": "PMID-9018153__text",
"type": "abstract",
"text": [
"Interaction of transcription factors RFX1 and MIBP1 with the gamma motif of the negative regulatory element of the hepatitis B virus core promoter. \nThe negative regulatory element (NRE) of the hepatitis B virus (HBV) core promoter contains three subregions which act synergistically to suppress core promoter activity. One of these subregions, NRE gamma, is active in both HeLa cervical carcinoma cells and Huh7 hepatoma cells and was found to be bound by a protein factor present in both cell types. Here we show that the transcription factor RFX1 can bind to NRE gamma and transactivate the core promoter through this site. Mutations which abrogated the gene-suppressive activity of NRE gamma prevented RFX1 from binding to NRE gamma. In addition, RFX1 can bind simultaneously, most likely as a heterodimer, with the transcription factor MIBP1 to NRE gamma. In the absence of a cloned MIBP1 gene for further studies, we hypothesize that RFX1 acts with MIBP1 to negatively regulate the core promoter activity through the NRE gamma site. The ability of RFX1 to transactivate the core promoter raises the possibility that RFX1 may play a dual role in regulating HBV gene expression.\n"
],
"offsets": [
[
0,
1183
]
]
}
] | [
{
"id": "PMID-9018153_T1",
"type": "Protein",
"text": [
"RFX1"
],
"offsets": [
[
37,
41
]
],
"normalized": []
},
{
"id": "PMID-9018153_T2",
"type": "Protein",
"text": [
"MIBP1"
],
"offsets": [
[
46,
51
]
],
"normalized": []
},
{
"id": "PMID-9018153_T3",
"type": "Protein",
"text": [
"RFX1"
],
"offsets": [
[
545,
549
]
],
"normalized": []
},
{
"id": "PMID-9018153_T4",
"type": "Protein",
"text": [
"RFX1"
],
"offsets": [
[
706,
710
]
],
"normalized": []
},
{
"id": "PMID-9018153_T5",
"type": "Protein",
"text": [
"RFX1"
],
"offsets": [
[
751,
755
]
],
"normalized": []
},
{
"id": "PMID-9018153_T6",
"type": "Protein",
"text": [
"MIBP1"
],
"offsets": [
[
841,
846
]
],
"normalized": []
},
{
"id": "PMID-9018153_T7",
"type": "Protein",
"text": [
"MIBP1"
],
"offsets": [
[
888,
893
]
],
"normalized": []
},
{
"id": "PMID-9018153_T8",
"type": "Protein",
"text": [
"RFX1"
],
"offsets": [
[
940,
944
]
],
"normalized": []
},
{
"id": "PMID-9018153_T9",
"type": "Protein",
"text": [
"MIBP1"
],
"offsets": [
[
955,
960
]
],
"normalized": []
},
{
"id": "PMID-9018153_T10",
"type": "Protein",
"text": [
"RFX1"
],
"offsets": [
[
1054,
1058
]
],
"normalized": []
},
{
"id": "PMID-9018153_T11",
"type": "Protein",
"text": [
"RFX1"
],
"offsets": [
[
1122,
1126
]
],
"normalized": []
}
] | [] | [] | [] |
73 | PMID-9119025 | [
{
"id": "PMID-9119025__text",
"type": "abstract",
"text": [
"Cell-to-cell contact activates the long terminal repeat of human immunodeficiency virus 1 through its kappaB motif. \nCell-to-cell contact between peripheral blood lymphocytes and transfected human colonic carcinoma cell line HT29 activates transcription of the long terminal repeats (LTR) of human immunodeficiency virus. HIV-1 LTR transcription is controlled by a complex array of virus-encoded and cellular proteins. Using various constructs expressing a lacZ reporter gene under the control of the intact or three deleted forms of HIV-1 LTR, we obtained evidence that the kappaB regulatory elements located in the U3 region are involved in cell-to-cell activation of HIV-1 LTR. Cell-to-cell contact activates in vitro binding of the nuclear factor kappaB (NF-kappaB) p50/p65 heterodimer to an HIV-1 kappaB oligonucleotide. Cell-to-cell contact activation of NF-kappaB was only partially inhibited by 100 microM pyrrolidine dithiocarbamate and was not correlated with a significant decrease of cellular inhibitor kappaB alpha. NF-kappaB nuclear activation was not detectable before 1 h after cell contact and was dependent on protein synthesis.\n"
],
"offsets": [
[
0,
1147
]
]
}
] | [
{
"id": "PMID-9119025_T1",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
770,
773
]
],
"normalized": []
},
{
"id": "PMID-9119025_T2",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
774,
777
]
],
"normalized": []
},
{
"id": "PMID-9119025_T3",
"type": "Protein",
"text": [
"inhibitor kappaB alpha"
],
"offsets": [
[
1005,
1027
]
],
"normalized": []
}
] | [] | [] | [] |
90 | PMID-7859743 | [
{
"id": "PMID-7859743__text",
"type": "abstract",
"text": [
"HIV-1 Tat potentiates TNF-induced NF-kappa B activation and cytotoxicity by altering the cellular redox state. \nThis study demonstrates that human immunodeficiency virus type 1 (HIV-1) Tat protein amplifies the activity of tumor necrosis factor (TNF), a cytokine that stimulates HIV-1 replication through activation of NF-kappa B. In HeLa cells stably transfected with the HIV-1 tat gene (HeLa-tat cells), expression of the Tat protein enhanced both TNF-induced activation of NF-kappa B and TNF-mediated cytotoxicity. A similar potentiation of TNF effects was observed in Jurkat T cells and HeLa cells treated with soluble Tat protein. TNF-mediated activation of NF-kappa B and cytotoxicity involves the intracellular formation of reactive oxygen intermediates. Therefore, Tat-mediated effects on the cellular redox state were analyzed. In both T cells and HeLa cells HIV-1 Tat suppressed the expression of Mn-dependent superoxide dismutase (Mn-SOD), a mitochondrial enzyme that is part of the cellular defense system against oxidative stress. Thus, Mn-SOD RNA protein levels and activity were markedly reduced in the presence of Tat. Decreased Mn-SOD expression was associated with decreased levels of glutathione and a lower ratio of reduced:oxidized glutathione. A truncated Tat protein (Tat1-72), known to transactivate the HIV-1 long terminal repeat (LTR), no longer affected Mn-SOD expression, the cellular redox state or TNF-mediated cytotoxicity. Thus, our experiments demonstrate that the C-terminal region of HIV-1 Tat is required to suppress Mn-SOD expression and to induce pro-oxidative conditions reflected by a drop in reduced glutathione (GSH) and the GSH:oxidized GSH (GSSG) ratio. (ABSTRACT TRUNCATED AT 250 WORDS)\n"
],
"offsets": [
[
0,
1732
]
]
}
] | [
{
"id": "PMID-7859743_T1",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
6,
9
]
],
"normalized": []
},
{
"id": "PMID-7859743_T2",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
185,
188
]
],
"normalized": []
},
{
"id": "PMID-7859743_T3",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
424,
427
]
],
"normalized": []
},
{
"id": "PMID-7859743_T4",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
623,
626
]
],
"normalized": []
},
{
"id": "PMID-7859743_T5",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
773,
776
]
],
"normalized": []
},
{
"id": "PMID-7859743_T6",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
874,
877
]
],
"normalized": []
},
{
"id": "PMID-7859743_T7",
"type": "Protein",
"text": [
"Mn-dependent superoxide dismutase"
],
"offsets": [
[
907,
940
]
],
"normalized": []
},
{
"id": "PMID-7859743_T8",
"type": "Protein",
"text": [
"Mn-SOD"
],
"offsets": [
[
942,
948
]
],
"normalized": []
},
{
"id": "PMID-7859743_T9",
"type": "Protein",
"text": [
"Mn-SOD"
],
"offsets": [
[
1050,
1056
]
],
"normalized": []
},
{
"id": "PMID-7859743_T10",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1130,
1133
]
],
"normalized": []
},
{
"id": "PMID-7859743_T11",
"type": "Protein",
"text": [
"Mn-SOD"
],
"offsets": [
[
1145,
1151
]
],
"normalized": []
},
{
"id": "PMID-7859743_T12",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1278,
1281
]
],
"normalized": []
},
{
"id": "PMID-7859743_T13",
"type": "Protein",
"text": [
"Mn-SOD"
],
"offsets": [
[
1381,
1387
]
],
"normalized": []
},
{
"id": "PMID-7859743_T14",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1525,
1528
]
],
"normalized": []
},
{
"id": "PMID-7859743_T15",
"type": "Protein",
"text": [
"Mn-SOD"
],
"offsets": [
[
1553,
1559
]
],
"normalized": []
}
] | [] | [] | [] |
93 | PMID-10233927 | [
{
"id": "PMID-10233927__text",
"type": "abstract",
"text": [
"Control of cell cycle entry and apoptosis in B lymphocytes infected by Epstein-Barr virus. \nInfection of human B cells with Epstein-Barr virus (EBV) results in activation of the cell cycle and cell growth. To interpret the mechanisms by which EBV activates the cell, we have assayed many proteins involved in control of the G0 and G1 phases of the cell cycle and regulation of apoptosis. In EBV infection most of the changes, including the early induction of cyclin D2, are dependent on expression of EBV genes, but an alteration in the E2F-4 profile was partly independent of viral gene expression, presumably occurring in response to signal transduction activated when the virus binds to its receptor, CD21. By comparing the expression of genes controlling apoptosis, including those encoding several members of the BCL-2 family of proteins, the known relative resistance of EBV-immortalized B-cell lines to apoptosis induced by low serum was found to correlate with expression of both BCL-2 and A20. A20 can be regulated by the NF-kappaB transcription factor, which is known to be activated by the EBV LMP-1 protein. Quantitative assays demonstrated a direct temporal relationship between LMP-1 protein levels and active NF-kappaB during the time course of infection.\n"
],
"offsets": [
[
0,
1271
]
]
}
] | [
{
"id": "PMID-10233927_T1",
"type": "Protein",
"text": [
"cyclin D2"
],
"offsets": [
[
459,
468
]
],
"normalized": []
},
{
"id": "PMID-10233927_T2",
"type": "Protein",
"text": [
"E2F-4"
],
"offsets": [
[
537,
542
]
],
"normalized": []
},
{
"id": "PMID-10233927_T3",
"type": "Protein",
"text": [
"CD21"
],
"offsets": [
[
704,
708
]
],
"normalized": []
},
{
"id": "PMID-10233927_T4",
"type": "Protein",
"text": [
"BCL-2"
],
"offsets": [
[
988,
993
]
],
"normalized": []
},
{
"id": "PMID-10233927_T5",
"type": "Protein",
"text": [
"A20"
],
"offsets": [
[
998,
1001
]
],
"normalized": []
},
{
"id": "PMID-10233927_T6",
"type": "Protein",
"text": [
"A20"
],
"offsets": [
[
1003,
1006
]
],
"normalized": []
},
{
"id": "PMID-10233927_T7",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
1105,
1110
]
],
"normalized": []
},
{
"id": "PMID-10233927_T8",
"type": "Protein",
"text": [
"LMP-1"
],
"offsets": [
[
1192,
1197
]
],
"normalized": []
}
] | [] | [] | [] |
94 | PMID-7659529 | [
{
"id": "PMID-7659529__text",
"type": "abstract",
"text": [
"Regulation of transcription of the human erythropoietin receptor gene by proteins binding to GATA-1 and Sp1 motifs. \nErythropoietin (Epo), the primary regulator of the production of erythroid cells, acts by binding to a cell surface receptor (EpoR) on erythroid progenitors. We used deletion analysis and transfection assays with reporter gene constructs to examine the transcription control elements in the 5' flanking region of the human EpoR gene. In erythroid cells most of the transcription activity was contained in a 150 bp promoter fragment with binding sites for transcription factors AP2, Sp1 and the erythroid-specific GATA-1. The 150 bp hEpoR promoter exhibited high and low activity in erythroid OCIM1 and K562 cells, respectively, reflecting the high and low levels of constitutive hEpoR expression. The GATA-1 and Sp1 binding sites in this promoter lacking a TATA sequence were necessary for a high level of transcription activation. Protein-DNA binding studies suggested that Sp1 and two other CCGCCC binding proteins from erythroid and non-erythroid cells could bind to the Sp1 binding motif. By increasing GATA-1 levels via co-transfection, we were able to transactivate the hEpoR promoter in K562 cells and non-erythroid cells, but not in the highly active OCIM1 cells, although GATA-1 mRNA levels were comparable in OCIM1 and K562. Interestingly, when we mutated the Sp1 site, resulting in a marked decrease in hEpoR promoter activity, we could restore transactivation by increasing GATA-1 levels in OCIM1 cells. These data suggest that while GATA-1 can transactivate the EpoR promoter, the level of hEpoR gene expression does not depend on GATA-1 alone. Rather, hEpoR transcription activity depends on coordination between Sp1 and GATA-1 with other cell-specific factors, including possibly other Sp1-like binding proteins, to provide high level, tissue-specific expression.\n"
],
"offsets": [
[
0,
1896
]
]
}
] | [
{
"id": "PMID-7659529_T1",
"type": "Protein",
"text": [
"erythropoietin receptor"
],
"offsets": [
[
41,
64
]
],
"normalized": []
},
{
"id": "PMID-7659529_T2",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
93,
99
]
],
"normalized": []
},
{
"id": "PMID-7659529_T3",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
104,
107
]
],
"normalized": []
},
{
"id": "PMID-7659529_T4",
"type": "Protein",
"text": [
"Erythropoietin"
],
"offsets": [
[
117,
131
]
],
"normalized": []
},
{
"id": "PMID-7659529_T5",
"type": "Protein",
"text": [
"Epo"
],
"offsets": [
[
133,
136
]
],
"normalized": []
},
{
"id": "PMID-7659529_T6",
"type": "Protein",
"text": [
"EpoR"
],
"offsets": [
[
243,
247
]
],
"normalized": []
},
{
"id": "PMID-7659529_T7",
"type": "Protein",
"text": [
"EpoR"
],
"offsets": [
[
440,
444
]
],
"normalized": []
},
{
"id": "PMID-7659529_T8",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
599,
602
]
],
"normalized": []
},
{
"id": "PMID-7659529_T9",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
630,
636
]
],
"normalized": []
},
{
"id": "PMID-7659529_T10",
"type": "Protein",
"text": [
"hEpoR"
],
"offsets": [
[
649,
654
]
],
"normalized": []
},
{
"id": "PMID-7659529_T11",
"type": "Protein",
"text": [
"hEpoR"
],
"offsets": [
[
796,
801
]
],
"normalized": []
},
{
"id": "PMID-7659529_T12",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
818,
824
]
],
"normalized": []
},
{
"id": "PMID-7659529_T13",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
829,
832
]
],
"normalized": []
},
{
"id": "PMID-7659529_T14",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
992,
995
]
],
"normalized": []
},
{
"id": "PMID-7659529_T15",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1091,
1094
]
],
"normalized": []
},
{
"id": "PMID-7659529_T16",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
1124,
1130
]
],
"normalized": []
},
{
"id": "PMID-7659529_T17",
"type": "Protein",
"text": [
"hEpoR"
],
"offsets": [
[
1193,
1198
]
],
"normalized": []
},
{
"id": "PMID-7659529_T18",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
1298,
1304
]
],
"normalized": []
},
{
"id": "PMID-7659529_T19",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1387,
1390
]
],
"normalized": []
},
{
"id": "PMID-7659529_T20",
"type": "Protein",
"text": [
"hEpoR"
],
"offsets": [
[
1431,
1436
]
],
"normalized": []
},
{
"id": "PMID-7659529_T21",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
1503,
1509
]
],
"normalized": []
},
{
"id": "PMID-7659529_T22",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
1563,
1569
]
],
"normalized": []
},
{
"id": "PMID-7659529_T23",
"type": "Protein",
"text": [
"EpoR"
],
"offsets": [
[
1592,
1596
]
],
"normalized": []
},
{
"id": "PMID-7659529_T24",
"type": "Protein",
"text": [
"hEpoR"
],
"offsets": [
[
1620,
1625
]
],
"normalized": []
},
{
"id": "PMID-7659529_T25",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
1661,
1667
]
],
"normalized": []
},
{
"id": "PMID-7659529_T26",
"type": "Protein",
"text": [
"hEpoR"
],
"offsets": [
[
1683,
1688
]
],
"normalized": []
},
{
"id": "PMID-7659529_T27",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1744,
1747
]
],
"normalized": []
},
{
"id": "PMID-7659529_T28",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
1752,
1758
]
],
"normalized": []
},
{
"id": "PMID-7659529_T29",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1818,
1821
]
],
"normalized": []
}
] | [] | [] | [] |
96 | PMID-8179594 | [
{
"id": "PMID-8179594__text",
"type": "abstract",
"text": [
"Effects of alpha-lipoic acid and dihydrolipoic acid on expression of proto-oncogene c-fos. \nThe transcription factor AP-1 is an important human mediator of the cellular response to serum, growth factors, and phorbol esters such as 12-O-tetradecanoyl-phorbol-13 acetate (TPA). The AP-1 complex consists of distinct protein heterodimers encoded by the proto-oncogene c-fos and c-jun mRNA whose gene expression can be induced by TPA, cyclic AMP and growth factors. Recent findings suggest an involvement of reactive oxygen species in the pathway of TPA and protein kinase C leading to expression of c-fos and c-jun mRNA. To investigate the role of reactive oxygen species we studied the effects of alpha-lipoic acid and dihydrolipoic acid (natural thiol antioxidants) on the expression of c-fos mRNA in human Jurkat T cells. When cells were preincubated with dihydrolipoic acid (0.2 mM) the expression of c-fos mRNA was suppressed at 30 min after stimulation of TPA (0.5 microM) whereas in the case of preincubation of alpha-lipoic acid (0.2 microM), the expression was enhanced at 30 min. These studies support the idea that superoxide anion radical plays a role in the expression of c-fos mRNA.\n"
],
"offsets": [
[
0,
1194
]
]
}
] | [
{
"id": "PMID-8179594_T1",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
84,
89
]
],
"normalized": []
},
{
"id": "PMID-8179594_T2",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
365,
370
]
],
"normalized": []
},
{
"id": "PMID-8179594_T3",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
375,
380
]
],
"normalized": []
},
{
"id": "PMID-8179594_T4",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
596,
601
]
],
"normalized": []
},
{
"id": "PMID-8179594_T5",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
606,
611
]
],
"normalized": []
},
{
"id": "PMID-8179594_T6",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
786,
791
]
],
"normalized": []
},
{
"id": "PMID-8179594_T7",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
902,
907
]
],
"normalized": []
},
{
"id": "PMID-8179594_T8",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
1182,
1187
]
],
"normalized": []
}
] | [] | [] | [] |
97 | PMID-8562886 | [
{
"id": "PMID-8562886__text",
"type": "abstract",
"text": [
"The effect of Toremifene on the expression of some genes in human mononuclear cells. \nToremifene exerts multiple and varied effects on the gene expression of human peripheral mononuclear cells. After short-term, in vitro exposure to therapeutical levels, distinct changes in P-glycoprotein, steroid receptors, p53 and Bcl-2 expression take place. In view of the increasing use of antiestrogens in cancer therapy and prevention, there is obvious merit in long-term in vivo studies to be conducted.\n"
],
"offsets": [
[
0,
497
]
]
}
] | [
{
"id": "PMID-8562886_T1",
"type": "Protein",
"text": [
"p53"
],
"offsets": [
[
310,
313
]
],
"normalized": []
},
{
"id": "PMID-8562886_T2",
"type": "Protein",
"text": [
"Bcl-2"
],
"offsets": [
[
318,
323
]
],
"normalized": []
}
] | [] | [] | [] |
98 | PMID-8725939 | [
{
"id": "PMID-8725939__text",
"type": "abstract",
"text": [
"Regulation of gene expression at early stages of B-cell and T-cell differentiation. \nThe expression of distinct sets of genes at different stages of B-lymphocyte and T-lymphocyte differentiation is controlled at the level of transcription. A number of recent studies have described interactions between transcription factors in lymphocytes that provide new insights into mechanisms regulating gene expression. These mechanisms include the assembly of higher order nucleoprotein complexes and other protein-protein interactions that enhance the functional specificity of transcriptional regulators in lymphocytes.\n"
],
"offsets": [
[
0,
613
]
]
}
] | [] | [] | [] | [] |
99 | PMID-8577772 | [
{
"id": "PMID-8577772__text",
"type": "abstract",
"text": [
"In vivo anergized CD4+ T cells express perturbed AP-1 and NF-kappa B transcription factors. \nAnergy is a major mechanism to ensure antigen-specific tolerance in T lymphocytes in the adult. In vivo, anergy has mainly been studied at the cellular level. In this study, we used the T-cell-activating superantigen staphylococcal enterotoxin A (SEA) to investigate molecular mechanisms of T-lymphocyte anergy in vivo. Injection of SEA to adult mice activates CD4+ T cells expressing certain T-cell receptor (TCR) variable region beta-chain families and induces strong and rapid production of interleukin 2 (IL-2). In contrast, repeated injections of SEA cause CD4+ T-cell deletion and anergy in the remaining CD4+ T cells, characterized by reduced expression of IL-2 at mRNA and protein levels. We analyzed expression of AP-1, NF-kappa B, NF-AT, and octamer binding transcription factors, which are known to be involved in the regulation of IL-2 gene promoter activity. Large amounts of AP-1 and NF-kappa B and significant quantities of NF-AT were induced in SEA-activated CD4+ spleen T cells, whereas Oct-1 and Oct-2 DNA binding activity was similar in both resting and activated T cells. In contrast, anergic CD4+ T cells contained severely reduced levels of AP-1 and Fos/Jun-containing NF-AT complexes but expressed significant amounts of NF-kappa B and Oct binding proteins after SEA stimulation. Resolution of the NF-kappa B complex demonstrated predominant expression of p50-p65 heterodimers in activated CD4+ T cells, while anergic cells mainly expressed the transcriptionally inactive p50 homodimer. These alterations of transcription factors are likely to be responsible for repression of IL-2 in anergic T cells.\n"
],
"offsets": [
[
0,
1718
]
]
}
] | [
{
"id": "PMID-8577772_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
18,
21
]
],
"normalized": []
},
{
"id": "PMID-8577772_T2",
"type": "Protein",
"text": [
"staphylococcal enterotoxin A"
],
"offsets": [
[
310,
338
]
],
"normalized": []
},
{
"id": "PMID-8577772_T3",
"type": "Protein",
"text": [
"SEA"
],
"offsets": [
[
340,
343
]
],
"normalized": []
},
{
"id": "PMID-8577772_T4",
"type": "Protein",
"text": [
"SEA"
],
"offsets": [
[
426,
429
]
],
"normalized": []
},
{
"id": "PMID-8577772_T5",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
454,
457
]
],
"normalized": []
},
{
"id": "PMID-8577772_T6",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
587,
600
]
],
"normalized": []
},
{
"id": "PMID-8577772_T7",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
602,
606
]
],
"normalized": []
},
{
"id": "PMID-8577772_T8",
"type": "Protein",
"text": [
"SEA"
],
"offsets": [
[
645,
648
]
],
"normalized": []
},
{
"id": "PMID-8577772_T9",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
655,
658
]
],
"normalized": []
},
{
"id": "PMID-8577772_T10",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
704,
707
]
],
"normalized": []
},
{
"id": "PMID-8577772_T11",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
757,
761
]
],
"normalized": []
},
{
"id": "PMID-8577772_T12",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
936,
940
]
],
"normalized": []
},
{
"id": "PMID-8577772_T13",
"type": "Protein",
"text": [
"SEA"
],
"offsets": [
[
1054,
1057
]
],
"normalized": []
},
{
"id": "PMID-8577772_T14",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
1068,
1071
]
],
"normalized": []
},
{
"id": "PMID-8577772_T15",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
1097,
1102
]
],
"normalized": []
},
{
"id": "PMID-8577772_T16",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
1107,
1112
]
],
"normalized": []
},
{
"id": "PMID-8577772_T17",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
1206,
1209
]
],
"normalized": []
},
{
"id": "PMID-8577772_T18",
"type": "Protein",
"text": [
"Fos"
],
"offsets": [
[
1265,
1268
]
],
"normalized": []
},
{
"id": "PMID-8577772_T19",
"type": "Protein",
"text": [
"Jun"
],
"offsets": [
[
1269,
1272
]
],
"normalized": []
},
{
"id": "PMID-8577772_T20",
"type": "Protein",
"text": [
"SEA"
],
"offsets": [
[
1379,
1382
]
],
"normalized": []
},
{
"id": "PMID-8577772_T21",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1472,
1475
]
],
"normalized": []
},
{
"id": "PMID-8577772_T22",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1476,
1479
]
],
"normalized": []
},
{
"id": "PMID-8577772_T23",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
1506,
1509
]
],
"normalized": []
},
{
"id": "PMID-8577772_T24",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1588,
1591
]
],
"normalized": []
},
{
"id": "PMID-8577772_T25",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1693,
1697
]
],
"normalized": []
}
] | [] | [] | [] |
103 | PMID-1645452 | [
{
"id": "PMID-1645452__text",
"type": "abstract",
"text": [
"The human myelomonocytic cell line U-937 as a model for studying alterations in steroid-induced monokine gene expression: marked enhancement of lipopolysaccharide-stimulated interleukin-1 beta messenger RNA levels by 1,25-dihydroxyvitamin D3. \nThe active metabolite of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], is a potent regulator of human monocyte/macrophage function in vitro. To establish a model for 1,25-(OH)2D3 regulation of human monocyte monokine synthesis, three human cell lines (U-937, THP-1, and HL-60) were examined for: 1) the presence of functional 1,25-(OH)2D3 receptors; 2) the accumulation of interleukin-1 beta (IL-1 beta) mRNA and IL-1 beta protein in response to lipopolysaccharide (LPS); and 3) the regulation of this response by 1,25-(OH)2D3. All three cell lines expressed vitamin D receptor and had increased levels of IL-1 beta mRNA in response to LPS. Preincubation of cells with 1,25-(OH)2D3 augmented IL-1 beta mRNA levels only in U-937 and HL-60 cells. From these data, and taking into consideration their state of differentiation and relative ease of culture, U-937 was chosen over HL-60 and THP-1 as the cell line we further characterized. In U-937 cells, optimum time and dose of pretreatment with 1,25-(OH)2D3 were determined to be 12-24 h at a receptor saturating concentration of 1,25-(OH)2D3 (10 nM). Preincubation of cells with 1,25-(OH)2D3 had no effect on the time course of IL-1 beta mRNA appearance in response to LPS. However, exposure of U-937 cells to 1,25-(OH)2D3 increased by 200% the level of IL-1 beta mRNA detected and decreased by three orders of magnitude the concentration of LPS required to achieve steady state mRNA levels equivalent to those observed in U-937 cells not preincubated with the hormone.2+o\n"
],
"offsets": [
[
0,
1772
]
]
}
] | [
{
"id": "PMID-1645452_T1",
"type": "Protein",
"text": [
"interleukin-1 beta"
],
"offsets": [
[
174,
192
]
],
"normalized": []
},
{
"id": "PMID-1645452_T2",
"type": "Protein",
"text": [
"interleukin-1 beta"
],
"offsets": [
[
623,
641
]
],
"normalized": []
},
{
"id": "PMID-1645452_T3",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
643,
652
]
],
"normalized": []
},
{
"id": "PMID-1645452_T4",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
663,
672
]
],
"normalized": []
},
{
"id": "PMID-1645452_T5",
"type": "Protein",
"text": [
"vitamin D receptor"
],
"offsets": [
[
809,
827
]
],
"normalized": []
},
{
"id": "PMID-1645452_T6",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
856,
865
]
],
"normalized": []
},
{
"id": "PMID-1645452_T7",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
942,
951
]
],
"normalized": []
},
{
"id": "PMID-1645452_T8",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
1427,
1436
]
],
"normalized": []
},
{
"id": "PMID-1645452_T9",
"type": "Protein",
"text": [
"IL-1 beta"
],
"offsets": [
[
1553,
1562
]
],
"normalized": []
}
] | [] | [] | [] |
106 | PMID-10233882 | [
{
"id": "PMID-10233882__text",
"type": "abstract",
"text": [
"An essential role for NF-kappaB in human CD34(+) bone marrow cell survival. \nThe transcription factor, NF-kappaB, is important for T-cell activation, B-cell maturation, and human immunodeficiency virus transcription and plays a role in alternatively mediating and protecting against apoptosis in a variety of cell types. However, a role for NF-kappaB in human CD34(+) bone marrow cells has not been described. We provide evidence here that virtually all human CD34(+) bone marrow cells express NF-kappaB that can be activated by exposure to phorbol 12-myristate 13-acetate and a variety of cytokines, eg, tumor necrosis factor alpha, interleukin-3, and granulocyte-macrophage colony-stimulating factor. In addition, we demonstrate that NF-kappaB may be required for human CD34(+) bone marrow cell clonogenic function and survival. These results offer insight into a new role for NF-kappaB in maintaining survival and function in hematopoietic stem and progenitor cells and suggest that proposed strategies involving inhibition of NF-kappaB activation as an adjunct to cancer chemotherapy should be approached with caution.\n"
],
"offsets": [
[
0,
1123
]
]
}
] | [
{
"id": "PMID-10233882_T1",
"type": "Protein",
"text": [
"CD34"
],
"offsets": [
[
41,
45
]
],
"normalized": []
},
{
"id": "PMID-10233882_T2",
"type": "Protein",
"text": [
"CD34"
],
"offsets": [
[
360,
364
]
],
"normalized": []
},
{
"id": "PMID-10233882_T3",
"type": "Protein",
"text": [
"CD34"
],
"offsets": [
[
460,
464
]
],
"normalized": []
},
{
"id": "PMID-10233882_T4",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
605,
632
]
],
"normalized": []
},
{
"id": "PMID-10233882_T5",
"type": "Protein",
"text": [
"interleukin-3"
],
"offsets": [
[
634,
647
]
],
"normalized": []
},
{
"id": "PMID-10233882_T6",
"type": "Protein",
"text": [
"granulocyte-macrophage colony-stimulating factor"
],
"offsets": [
[
653,
701
]
],
"normalized": []
},
{
"id": "PMID-10233882_T7",
"type": "Protein",
"text": [
"CD34"
],
"offsets": [
[
772,
776
]
],
"normalized": []
}
] | [] | [] | [] |
108 | PMID-8960112 | [
{
"id": "PMID-8960112__text",
"type": "abstract",
"text": [
"Lymphocytes from CML patients lack a 47 kDa factor having affinity for a genomic sterol regulatory sequence. \nDeranged cellular cholesterol homeostasis has been widely recognized in the initiation as well as progression of various types of cancers including chronic myeloid leukaemia (CML). Since the human genomic sterol regulatory element (SRE) has been shown to regulate various key genes involved in this phenomenon, the present study revealed the existence of a unique 47 kDa protein factor having affinity for this SRE sequence in lymphocytes from normal subjects, as well as its absence in lymphocytes from untreated CML patients. However, this factor appeared when these CML patients achieved complete haematological remission (CHR) through alpha-interferon therapy. Furthermore, an inverse relationship was also observed between the LDL receptor gene expression at the transcriptional level and the binding affinity of this 47 kDa protein factor to the SRE sequence. Based upon these results we propose that this factor may have a role in pathophysiology of chronic myeloid leukaemia.\n"
],
"offsets": [
[
0,
1094
]
]
}
] | [
{
"id": "PMID-8960112_T1",
"type": "Protein",
"text": [
"LDL receptor"
],
"offsets": [
[
842,
854
]
],
"normalized": []
}
] | [] | [] | [] |
111 | PMID-7890658 | [
{
"id": "PMID-7890658__text",
"type": "abstract",
"text": [
"Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter [published erratum appears in J Biol Chem 1995 Nov 3;270(44):26721] \nA DNA response element (TR2RE-SV40) for the TR2 orphan receptor, a member of the steroid-thyroid hormone receptor superfamily, has been identified in the simian virus 40 (SV40) +55 region (nucleotide numbers 368-389, 5'-GTTAAGGTTCGTAGGTCATGGA-3'). Electrophoretic mobility shift assay, using in vitro translated TR2 orphan receptor with a molecular mass of 67 kilodaltons, showed a specific binding with high affinity (dissociation constant = 9 nM) for this DNA sequence. DNA-swap experiments using chloramphenicol acetyl-transferase assay demonstrated that androgen can suppress the transcriptional activities of SV40 early promoter via the interaction between this TR2RE-SV40 and the chimeric receptor AR/TR2/AR with the DNA-binding domain of the TR2 orphan receptor flanked by the N-terminal and androgen-binding domains of the androgen receptor. In addition, this TR2RE-SV40 can function as a repressor to suppress the transcriptional activities of both SV40 early and late promoters. Together, these data suggest the TR2RE-SV40 may represent the first identified natural DNA response element for the TR2 orphan receptor that may function as a repressor for the SV40 gene expression.\n"
],
"offsets": [
[
0,
1400
]
]
}
] | [
{
"id": "PMID-7890658_T1",
"type": "Protein",
"text": [
"chloramphenicol acetyl-transferase"
],
"offsets": [
[
711,
745
]
],
"normalized": []
}
] | [] | [] | [] |
112 | PMID-8871649 | [
{
"id": "PMID-8871649__text",
"type": "abstract",
"text": [
"A critical role of Sp1- and Ets-related transcription factors in maintaining CTL-specific expression of the mouse perforin gene. \nThis study was designed to determine the potential cis-elements involved in transcriptional regulation of the mouse perforin gene. DNase I hypersensitive site (DHS) mapping revealed that the perforin locus contained six DHS within 7.0 kb of the 5' upstream sequence (-7.0 kb) and two DHS in intron 2. The six 5' upstream and one intronic DHS were detected in only perforin-expressing lymphocytes. Chloramphenicol acetyltransferase (CAT) activities directed by 5' upstream promoter were detected preferentially in perforin-expressing cell lines. A construct termed PFP5a containing -795 bp exhibited the highest CAT activity, and PFP9a20 containing only -73 bp also produced significantly high CAT activity in CTLL-R8 cells. The proximal region in PFP9a20 contained two potential Sp1 binding sites (GC box and GT box) and one Ets binding site (EBS). Electrophoretic mobility shift assay showed that each of the cis-elements bound specific protein factors. When single-point mutation was introduced to each GC box, EBS, and GT box in PFP9a20, at least 3-fold less CAT activity was observed in CTLL-R8 cells. To confirm the importance of the three cis-acting elements in the perforin gene expression, point mutation was introduced again to each proximal GC box, EBS, and GT box of PFP5a. The point mutations resulted in a 2.5- to 3-fold reduction of CAT activity. The results suggest that a combination of the three proximal cis-acting elements may constitute a minimal region responsible for CTL-specific expression of perforin.\n"
],
"offsets": [
[
0,
1657
]
]
}
] | [
{
"id": "PMID-8871649_T1",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
19,
22
]
],
"normalized": []
},
{
"id": "PMID-8871649_T2",
"type": "Protein",
"text": [
"perforin"
],
"offsets": [
[
114,
122
]
],
"normalized": []
},
{
"id": "PMID-8871649_T3",
"type": "Protein",
"text": [
"perforin"
],
"offsets": [
[
246,
254
]
],
"normalized": []
},
{
"id": "PMID-8871649_T4",
"type": "Protein",
"text": [
"perforin"
],
"offsets": [
[
321,
329
]
],
"normalized": []
},
{
"id": "PMID-8871649_T5",
"type": "Protein",
"text": [
"perforin"
],
"offsets": [
[
494,
502
]
],
"normalized": []
},
{
"id": "PMID-8871649_T6",
"type": "Protein",
"text": [
"Chloramphenicol acetyltransferase"
],
"offsets": [
[
527,
560
]
],
"normalized": []
},
{
"id": "PMID-8871649_T7",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
562,
565
]
],
"normalized": []
},
{
"id": "PMID-8871649_T8",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
741,
744
]
],
"normalized": []
},
{
"id": "PMID-8871649_T9",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
823,
826
]
],
"normalized": []
},
{
"id": "PMID-8871649_T10",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
909,
912
]
],
"normalized": []
},
{
"id": "PMID-8871649_T11",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1192,
1195
]
],
"normalized": []
},
{
"id": "PMID-8871649_T12",
"type": "Protein",
"text": [
"perforin"
],
"offsets": [
[
1302,
1310
]
],
"normalized": []
},
{
"id": "PMID-8871649_T13",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1477,
1480
]
],
"normalized": []
},
{
"id": "PMID-8871649_T14",
"type": "Protein",
"text": [
"perforin"
],
"offsets": [
[
1647,
1655
]
],
"normalized": []
}
] | [] | [] | [] |
113 | PMID-7525701 | [
{
"id": "PMID-7525701__text",
"type": "abstract",
"text": [
"Cross-linking CD40 on B cells rapidly activates nuclear factor-kappa B. \nThe B cell-associated surface molecule CD40 functions to regulate B cell responses. Cross-linking CD40 on B cells can lead to homotypic cell adhesion, IL-6 production, and, in combination with cytokines, to Ig isotype switching. Tyrosine kinase activity is increased shortly after engagement of this receptor. Little is known about how the very early events induced by CD40 cross-linking link to cellular responses. In this study, we demonstrate that nuclear factor (NF)-kappa B and NF-kappa B-like transcription factors are activated after cross-linking CD40 on resting human tonsillar B cells and on B cell lines. The activation is rapid and is mediated through a tyrosine kinase-dependent pathway. The complexes detected in electrophoretic mobility shift assays contain p50, p65 (RelA), c-Rel, and most likely other components. By using transient transfection assays, we found that cross-linking CD40 supports NF-kappa B-dependent gene expression. Our results define the NF-kappa B system as an intermediate event in CD40 signaling and suggest that the CD40 pathway can influence the expression of B cell-associated genes with NF-kappa B consensus sites.\n"
],
"offsets": [
[
0,
1231
]
]
}
] | [
{
"id": "PMID-7525701_T1",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
14,
18
]
],
"normalized": []
},
{
"id": "PMID-7525701_T2",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
112,
116
]
],
"normalized": []
},
{
"id": "PMID-7525701_T3",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
171,
175
]
],
"normalized": []
},
{
"id": "PMID-7525701_T4",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
224,
228
]
],
"normalized": []
},
{
"id": "PMID-7525701_T5",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
442,
446
]
],
"normalized": []
},
{
"id": "PMID-7525701_T6",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
628,
632
]
],
"normalized": []
},
{
"id": "PMID-7525701_T7",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
846,
849
]
],
"normalized": []
},
{
"id": "PMID-7525701_T8",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
851,
854
]
],
"normalized": []
},
{
"id": "PMID-7525701_T9",
"type": "Protein",
"text": [
"RelA"
],
"offsets": [
[
856,
860
]
],
"normalized": []
},
{
"id": "PMID-7525701_T10",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
863,
868
]
],
"normalized": []
},
{
"id": "PMID-7525701_T11",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
972,
976
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],
"normalized": []
},
{
"id": "PMID-7525701_T12",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
1093,
1097
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],
"normalized": []
},
{
"id": "PMID-7525701_T13",
"type": "Protein",
"text": [
"CD40"
],
"offsets": [
[
1129,
1133
]
],
"normalized": []
}
] | [] | [] | [] |
120 | PMID-2278044 | [
{
"id": "PMID-2278044__text",
"type": "abstract",
"text": [
"Functional analysis of cis-linked regulatory sequences in the HLA DRA promoter by transcription in vitro. \nTwo consensus sequences, called X and Y boxes, capable of binding nuclear proteins and regulating expression in B cells have been defined within the immediate upstream region of major histocompatibility complex (MHC) class II promoters. Unlike other class II promoters, the HLA-DR alpha (DRA) promoter also contains one element identical to the \"octamer\" motif of immunoglobulin variable region promoters that is responsible for B cell-specific transcription. This \"octamer\" in the context of DRA appears capable of binding both the ubiquitous (OTF-1) and lymphoid-specific (OTF-2) \"octamer\" binding proteins, but at least one other distinct \"octamer\" complex was found. In order to characterize the function of cis-acting elements, we have developed an in vitro system in which a DRA promoter construct is transcribed more efficiently in extracts from B cells than in extracts from class II-negative HeLa cells. 5' deletion constructs which lacked the Y box, but retained the \"octamer\" motif and TATA box were completely inactive, and internal deletion of the Y box reduced transcription by 95%. Using supercoiled, but not linear templates, we observed differences in transcription efficiencies from templates lacking or disrupting the X consensus element that reflect effects of random replacement of X box sequences in transient expression assays. Demonstration of the complete dependence on the Y box in this system suggests that, despite its demonstrated importance in the DRA promoter, the DRA \"octamer\" does not utilize OTF-2 in a manner analogous to immunoglobulin promoters in B cells.\n"
],
"offsets": [
[
0,
1702
]
]
}
] | [
{
"id": "PMID-2278044_T1",
"type": "Protein",
"text": [
"OTF-1"
],
"offsets": [
[
652,
657
]
],
"normalized": []
},
{
"id": "PMID-2278044_T2",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
682,
687
]
],
"normalized": []
},
{
"id": "PMID-2278044_T3",
"type": "Protein",
"text": [
"OTF-2"
],
"offsets": [
[
1634,
1639
]
],
"normalized": []
}
] | [] | [] | [] |
123 | PMID-9765295 | [
{
"id": "PMID-9765295__text",
"type": "abstract",
"text": [
"Fcgamma receptor-mediated mitogen-activated protein kinase activation in monocytes is independent of Ras. \nReceptors for the Fc portion of immunoglobulin molecules (FcR) present on leukocyte cell membranes mediate a large number of cellular responses that are very important in host defense, including phagocytosis, cell cytotoxicity, production and secretion of inflammatory mediators, and modulation of the immune response. Cross-linking of FcR with immune complexes leads, first to activation of protein-tyrosine kinases. The molecular events that follow and that transduce signals from these receptors to the nucleus are still poorly defined. We have investigated the signal transduction pathway from Fc receptors that leads to gene activation and production of cytokines in monocytes. Cross-linking of FcR, on the THP-1 monocytic cell line, by immune complexes resulted in both activation of the transcription factor NF-kappaB and interleukin 1 production. These responses were completely blocked by tyrosine kinase inhibitors. In contrast, expression of dominant negative mutants of Ras and Raf-1, in these cells, did not have any effect on FcR-mediated nuclear factor activation, suggesting that the mitogen-activated protein kinase (MAPK) signaling pathway was not used by these receptors. However, MAPK activation was easily detected by in vitro kinase assays, after FcR cross-linking with immune complexes. Using the specific MAPK/extracellular signal-regulated kinase kinase (MAPK kinase) inhibitor PD98059, we found that MAPK activation is necessary for FcR-dependent activation of the nuclear factor NF-kappaB. These results strongly suggest that the signaling pathway from Fc receptors leading to expression of different genes important to leukocyte biology, initiates with tyrosine kinases and requires MAPK activation; but in contrast to other tyrosine kinase receptors, FcR-mediated MAPK activation does not involve Ras and Raf.\n"
],
"offsets": [
[
0,
1946
]
]
}
] | [
{
"id": "PMID-9765295_T1",
"type": "Protein",
"text": [
"Raf-1"
],
"offsets": [
[
1097,
1102
]
],
"normalized": []
}
] | [] | [] | [] |
124 | PMID-1956769 | [
{
"id": "PMID-1956769__text",
"type": "abstract",
"text": [
"Identification of transcriptional suppressor proteins that bind to the negative regulatory element of the human immunodeficiency virus type 1. \nTwo different proteins which independently bound to neighboring sequences within the negative regulatory element (NRE) of human immunodeficiency virus type 1 (HIV-1) were detected in the nuclear extract of a virus-infected human T cell line. One of the factors bound to a novel dyad symmetrical sequence. This sequence is well conserved in various HIV-1 isolates and partial homology was found with the promoter region of the human retinoblastoma gene. Similar DNA binding activity was detected in a variety of virus-uninfected human T cell lines and HeLa cells by means of a gel mobility shift assay. The other factor bound to a putative AP-1 recognition sequence predicted for the HIV-1 NRE. However, this factor did not bind to a typical AP-1 site. The insertion of multiple copies of the binding site for the former or latter factor into a heterologous promoter reduced the promoter activity to one-tenth or one-third, respectively. Thus, each factor may function as a novel negative regulator of transcription.\n"
],
"offsets": [
[
0,
1160
]
]
}
] | [] | [] | [] | [] |
125 | PMID-7635985 | [
{
"id": "PMID-7635985__text",
"type": "abstract",
"text": [
"Interleukin 4 activates a signal transducer and activator of transcription (Stat) protein which interacts with an interferon-gamma activation site-like sequence upstream of the I epsilon exon in a human B cell line. Evidence for the involvement of Janus kinase 3 and interleukin-4 Stat. \nGerm line C transcripts can be induced by IL-4 in the human B cell line, BL-2. Utilizing a IFN-gamma activation site-like DNA sequence element located upstream of the I epsilon exon, we demonstrated by gel mobility shift assays that IL-4 induced a binding activity in the cytosol and nucleus of BL-2 cells. This factor was designated IL-4 NAF (IL-4-induced nuclear-activating factors) and was identified as a tyrosine phosphoprotein, which translocates from the cytosol to the nucleus upon IL-4 treatment. Because these are the characteristics of a signal transducer and activator of transcription (Stat) protein, we determined whether antibodies to Stat proteins will interfere with gel mobility shift and found that antibodies to IL-4 Stat, also known as Stat6, but not antibodies to other Stat proteins, interfere with the formation of the IL-4 NAF complex. Congruous with the involvement of a Stat protein, IL-4 induced robust Janus kinase 3 (JAK3) activity in BL-2 cells. Cotransfection of JAK3 with IL-4 Stat into COS-7 cells produced an intracellular activity which bound the same IFN-gamma activation site-like sequence and comigrated with IL-4 NAF in electrophoretic mobility shift assay. These results show that IL-4 NAF is IL-4 Stat, which is activated by JAK3 in response to IL-4 receptor engagement.\n"
],
"offsets": [
[
0,
1601
]
]
}
] | [
{
"id": "PMID-7635985_T1",
"type": "Protein",
"text": [
"Interleukin 4"
],
"offsets": [
[
0,
13
]
],
"normalized": []
},
{
"id": "PMID-7635985_T2",
"type": "Protein",
"text": [
"interferon-gamma"
],
"offsets": [
[
114,
130
]
],
"normalized": []
},
{
"id": "PMID-7635985_T3",
"type": "Protein",
"text": [
"Janus kinase 3"
],
"offsets": [
[
248,
262
]
],
"normalized": []
},
{
"id": "PMID-7635985_T4",
"type": "Protein",
"text": [
"interleukin-4"
],
"offsets": [
[
267,
280
]
],
"normalized": []
},
{
"id": "PMID-7635985_T5",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
330,
334
]
],
"normalized": []
},
{
"id": "PMID-7635985_T6",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
379,
388
]
],
"normalized": []
},
{
"id": "PMID-7635985_T7",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
521,
525
]
],
"normalized": []
},
{
"id": "PMID-7635985_T8",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
622,
626
]
],
"normalized": []
},
{
"id": "PMID-7635985_T9",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
632,
636
]
],
"normalized": []
},
{
"id": "PMID-7635985_T10",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
778,
782
]
],
"normalized": []
},
{
"id": "PMID-7635985_T11",
"type": "Protein",
"text": [
"IL-4 Stat"
],
"offsets": [
[
1020,
1029
]
],
"normalized": []
},
{
"id": "PMID-7635985_T12",
"type": "Protein",
"text": [
"Stat6"
],
"offsets": [
[
1045,
1050
]
],
"normalized": []
},
{
"id": "PMID-7635985_T13",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1131,
1135
]
],
"normalized": []
},
{
"id": "PMID-7635985_T14",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1199,
1203
]
],
"normalized": []
},
{
"id": "PMID-7635985_T15",
"type": "Protein",
"text": [
"Janus kinase 3"
],
"offsets": [
[
1219,
1233
]
],
"normalized": []
},
{
"id": "PMID-7635985_T16",
"type": "Protein",
"text": [
"JAK3"
],
"offsets": [
[
1235,
1239
]
],
"normalized": []
},
{
"id": "PMID-7635985_T17",
"type": "Protein",
"text": [
"JAK3"
],
"offsets": [
[
1283,
1287
]
],
"normalized": []
},
{
"id": "PMID-7635985_T18",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1293,
1297
]
],
"normalized": []
},
{
"id": "PMID-7635985_T19",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
1376,
1385
]
],
"normalized": []
},
{
"id": "PMID-7635985_T20",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1436,
1440
]
],
"normalized": []
},
{
"id": "PMID-7635985_T21",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1510,
1514
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],
"normalized": []
},
{
"id": "PMID-7635985_T22",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1522,
1526
]
],
"normalized": []
},
{
"id": "PMID-7635985_T23",
"type": "Protein",
"text": [
"JAK3"
],
"offsets": [
[
1555,
1559
]
],
"normalized": []
},
{
"id": "PMID-7635985_T24",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1575,
1579
]
],
"normalized": []
}
] | [] | [] | [] |
126 | PMID-9428992 | [
{
"id": "PMID-9428992__text",
"type": "abstract",
"text": [
"Constitutive expression c-fos, c-jun, and NF kappa B mRNA is in nucleated fetal blood cells and up-regulation of c-fos and c-jun with anti-CD3 stimulation. \nFetal and neonatal lymphocytes are relatively resistant to activation and cytokine production when stimulated either via their T-cell antigen receptors or lectins. The molecular mechanism(s) responsible for this phenomenon have not been clearly elucidated. We have hypothesized that such defects in fetal/neonatal T-cell activation may be due to lack of expression of the transcriptional regulatory elements required for T-cell activation. We used reverse transcriptase-polymerase chain reaction to examine both fetal and term neonatal cord bloods for mRNA expression of three transcription factors implicated in T-cell activation: c-jun, c-fos, and NF kappa B (p50 subunit). We demonstrate that mRNAs for all three of these regulatory factors are expressed in fetal blood cells by the 27th week of gestation and in term cord bloods. Activation of term infant cord blood mononuclear cells with anti-CD3 monoclonal antibodies resulted in up-regulation of both c-jun and c-fos mRNAs within 15 min of stimulation. However, secretion of IL-2 by anti-CD3-stimulated cord blood mononuclear cells was still blunted compared with control cells from adults. We conclude that fetal nucleated blood cells constitutively express important genes for cytokine regulation and are able to increase intracellular accumulation of the mRNAs for these factors in response to anti-CD3 stimulation. Thus, qualitative differences in the capacity to regulate these factors could not be shown in fetal blood cells. Quantitative experiments comparing binding of these transcription factors to the IL-2 promoter are currently under investigation.\n"
],
"offsets": [
[
0,
1777
]
]
}
] | [
{
"id": "PMID-9428992_T1",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
24,
29
]
],
"normalized": []
},
{
"id": "PMID-9428992_T2",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
31,
36
]
],
"normalized": []
},
{
"id": "PMID-9428992_T3",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
113,
118
]
],
"normalized": []
},
{
"id": "PMID-9428992_T4",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
123,
128
]
],
"normalized": []
},
{
"id": "PMID-9428992_T5",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
789,
794
]
],
"normalized": []
},
{
"id": "PMID-9428992_T6",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
796,
801
]
],
"normalized": []
},
{
"id": "PMID-9428992_T7",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
819,
822
]
],
"normalized": []
},
{
"id": "PMID-9428992_T8",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1116,
1121
]
],
"normalized": []
},
{
"id": "PMID-9428992_T9",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
1126,
1131
]
],
"normalized": []
},
{
"id": "PMID-9428992_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1190,
1194
]
],
"normalized": []
},
{
"id": "PMID-9428992_T11",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1728,
1732
]
],
"normalized": []
}
] | [] | [] | [] |
132 | PMID-9725220 | [
{
"id": "PMID-9725220__text",
"type": "abstract",
"text": [
"Transcription of a minimal promoter from the NF-IL6 gene is regulated by CREB/ATF and SP1 proteins in U937 promonocytic cells. \nNF-IL6 is an important transcriptional regulator of genes induced in activated monocytes/macrophages, and NF-IL6 is the only CCAAT/enhancer-binding protein (C/EBP) family member whose steady-state mRNA levels increase upon activation of monocytes (1). We show that increased transcription of the NF-IL6 gene is responsible, at least in part, for induction of NF-IL6 mRNA following activation of U937 promonocytic cells. We have identified a 104-bp minimal promoter region of the NF-IL6 gene that is sufficient for basal and activation-dependent induction of transcription in U937 cells. This region contains binding sites for the cAMP response element-binding protein/activation transcription factor (CREB/ATF) and Sp1 families of transcription factors. Each site is functionally important and contributes independently to transcription of the NF-IL6 gene in U937 cells.\n"
],
"offsets": [
[
0,
999
]
]
}
] | [
{
"id": "PMID-9725220_T1",
"type": "Protein",
"text": [
"NF-IL6"
],
"offsets": [
[
45,
51
]
],
"normalized": []
},
{
"id": "PMID-9725220_T2",
"type": "Protein",
"text": [
"SP1"
],
"offsets": [
[
86,
89
]
],
"normalized": []
},
{
"id": "PMID-9725220_T3",
"type": "Protein",
"text": [
"NF-IL6"
],
"offsets": [
[
128,
134
]
],
"normalized": []
},
{
"id": "PMID-9725220_T4",
"type": "Protein",
"text": [
"NF-IL6"
],
"offsets": [
[
234,
240
]
],
"normalized": []
},
{
"id": "PMID-9725220_T5",
"type": "Protein",
"text": [
"NF-IL6"
],
"offsets": [
[
424,
430
]
],
"normalized": []
},
{
"id": "PMID-9725220_T6",
"type": "Protein",
"text": [
"NF-IL6"
],
"offsets": [
[
487,
493
]
],
"normalized": []
},
{
"id": "PMID-9725220_T7",
"type": "Protein",
"text": [
"NF-IL6"
],
"offsets": [
[
607,
613
]
],
"normalized": []
},
{
"id": "PMID-9725220_T8",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
843,
846
]
],
"normalized": []
},
{
"id": "PMID-9725220_T9",
"type": "Protein",
"text": [
"NF-IL6"
],
"offsets": [
[
972,
978
]
],
"normalized": []
}
] | [] | [] | [] |
136 | PMID-2105946 | [
{
"id": "PMID-2105946__text",
"type": "abstract",
"text": [
"Transcriptional and post-transcriptional regulation of c-jun expression during monocytic differentiation of human myeloid leukemic cells. \nAP-1, the polypeptide product of c-jun, recognizes and binds to specific DNA sequences and stimulates transcription of genes responsive to certain growth factors and phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). We studied the effects of TPA on the regulation of c-jun gene expression in HL-60 cells during monocytic differentiation. Low levels of c-jun transcripts were detectable in untreated HL-60 leukemic cells, increased significantly by 6 h, and reached near maximal levels by 24 h of exposure to 32 nM TPA. Similar kinetics of c-jun induction by TPA were observed in human U-937 and THP-1 monocytic leukemia cells. Similar findings were obtained with bryostatin 1 (10 nM), another activator of protein kinase C and inducer of monocytic differentiation. Furthermore, 1,25-dihydroxyvitamin D3 (0.5 microM), a structurally distinct agent which also induces HL-60 monocytic differentiation, increased c-jun expression. TPA treatment of HL-60 cells in the presence of cycloheximide was associated with superinduction of c-jun transcripts. Run-on analysis demonstrated detectable levels of c-jun gene transcription in untreated HL-60 cells, and that exposure to TPA increases this rate 3.3-fold. Treatment of HL-60 cells with both TPA and cycloheximide had no effect on the rates of c-jun transcription. The half-life of c-jun RNA as determined by treating HL-60 cells with TPA and actinomycin D was 30 min. In contrast, the half-life of c-jun RNA in TPA-treated HL-60 cells exposed to cycloheximide and actinomycin D was greater than 2 h. These findings suggested that the increase in c-jun RNA observed during TPA-induced monocytic differentiation is mediated by both transcriptional and post-transcriptional mechanisms.\n"
],
"offsets": [
[
0,
1885
]
]
}
] | [
{
"id": "PMID-2105946_T1",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
55,
60
]
],
"normalized": []
},
{
"id": "PMID-2105946_T2",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
172,
177
]
],
"normalized": []
},
{
"id": "PMID-2105946_T3",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
423,
428
]
],
"normalized": []
},
{
"id": "PMID-2105946_T4",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
508,
513
]
],
"normalized": []
},
{
"id": "PMID-2105946_T5",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
695,
700
]
],
"normalized": []
},
{
"id": "PMID-2105946_T6",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1065,
1070
]
],
"normalized": []
},
{
"id": "PMID-2105946_T7",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1183,
1188
]
],
"normalized": []
},
{
"id": "PMID-2105946_T8",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1252,
1257
]
],
"normalized": []
},
{
"id": "PMID-2105946_T9",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1445,
1450
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],
"normalized": []
},
{
"id": "PMID-2105946_T10",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1483,
1488
]
],
"normalized": []
},
{
"id": "PMID-2105946_T11",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1600,
1605
]
],
"normalized": []
},
{
"id": "PMID-2105946_T12",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
1748,
1753
]
],
"normalized": []
}
] | [] | [] | [] |
138 | PMID-1907460 | [
{
"id": "PMID-1907460__text",
"type": "abstract",
"text": [
"Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives. \nHIV-1 proviral DNA contains two binding sites for the transcription factor NF-kappa B. HIV-1-infected individuals have, on average, abnormally high levels of tumour necrosis factor alpha (TNF alpha) and abnormally low plasma cysteine levels. We therefore investigated the effects of cysteine and related thiols on HIV-1 replication and NF-kappa B expression. The experiments in this report show that cysteine or N-acetylcysteine (NAC) raise the intracellular glutathione (GSH) level and inhibit HIV-1 replication in persistently infected Molt-4 and U937 cells. However, inhibition of HIV-1 replication appears not to be directly correlated with GSH levels. Cysteine and NAC also inhibit NF-kappa B activity as determined by electrophoretic mobility shift assays and chloramphenicol acetyl-transferase (CAT) gene expression under control of NF-kappa B binding sites in uninfected cells. This suggests that the cysteine deficiency in HIV-1-infected individuals may cause an over-expression of NF-kappa B-dependent genes and enhance HIV-1 replication. NAC may be considered for the treatment of HIV-1-infected individuals.\n"
],
"offsets": [
[
0,
1215
]
]
}
] | [
{
"id": "PMID-1907460_T1",
"type": "Protein",
"text": [
"tumour necrosis factor alpha"
],
"offsets": [
[
253,
281
]
],
"normalized": []
},
{
"id": "PMID-1907460_T2",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
283,
292
]
],
"normalized": []
},
{
"id": "PMID-1907460_T3",
"type": "Protein",
"text": [
"chloramphenicol acetyl-transferase"
],
"offsets": [
[
861,
895
]
],
"normalized": []
},
{
"id": "PMID-1907460_T4",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
897,
900
]
],
"normalized": []
}
] | [] | [] | [] |
143 | PMID-9032265 | [
{
"id": "PMID-9032265__text",
"type": "abstract",
"text": [
"Transcriptional regulation of the ferritin heavy-chain gene: the activity of the CCAAT binding factor NF-Y is modulated in heme-treated Friend leukemia cells and during monocyte-to-macrophage differentiation. \nThe ferritin H-chain gene promoter regulation was analyzed in heme-treated Friend leukemia cells (FLCs) and during monocyte-to-macrophage differentiation. In the majority of cell lines studied, the regulation of ferritin expression was exerted mostly at the translational level. However, in differentiating erythroid cells, which must incorporate high levels of iron to sustain hemoglobin synthesis, and in macrophages, which are involved in iron storage, transcriptional regulation seemed to be a relevant mechanism. We show here that the minimum region of the ferritin H-gene promoter that is able to confer transcriptional regulation by heme in FLCs to a reporter gene is 77 nucleotides upstream of the TATA box. This cis element binds a protein complex referred to as HRF (heme-responsive factor), which is greatly enhanced both in heme-treated FLCs and during monocyte-to-macrophage differentiation. The CCAAT element present in reverse orientation in this promoter region of the ferritin H-chain gene is necessary for binding and for gene activity, since a single point mutation is able to abolish the binding of HRF and the transcriptional activity in transfected cells. By competition experiments and supershift assays, we identified the induced HRF as containing at least the ubiquitous transcription factor NF-Y. NF-Y is formed by three subunits, A, B, and C, all of which are necessary for DNA binding. Cotransfection with a transdominant negative mutant of the NF-YA subunit abolishes the transcriptional activation by heme, indicating that NF-Y plays an essential role in this activation. We have also observed a differential expression of the NF-YA subunit in heme-treated and control FLCs and during monocyte-to-macrophage differentiation.\n"
],
"offsets": [
[
0,
1965
]
]
}
] | [
{
"id": "PMID-9032265_T1",
"type": "Protein",
"text": [
"ferritin H-chain"
],
"offsets": [
[
214,
230
]
],
"normalized": []
},
{
"id": "PMID-9032265_T2",
"type": "Protein",
"text": [
"ferritin H"
],
"offsets": [
[
772,
782
]
],
"normalized": []
},
{
"id": "PMID-9032265_T3",
"type": "Protein",
"text": [
"ferritin H-chain"
],
"offsets": [
[
1195,
1211
]
],
"normalized": []
}
] | [] | [] | [] |
144 | PMID-9837745 | [
{
"id": "PMID-9837745__text",
"type": "abstract",
"text": [
"Interleukin-12 expression in B cells by transformation with Epstein-Barr virus. \nAlthough interleukin (IL)-12 was originally purified from an Epstein-Barr (EBV)-transformed B cell line and the high correlation of EBV infection and IL-12 expression has been suggested, no study has reported whether EBV infection is directly linked to IL-12 expression. To address this issue, we have investigated IL-12 expression in B cells during in vitro transformation with EBV. Human peripheral B cells became capable of constitutively producing p40 by in vitro transformation with EBV, coincident with the expression of latent membrane protein 1 (LMP1) of EBV. These B cells expressed p40 and p35 mRNA, and phorbol myristate acetate (PMA) stimulation strongly enhanced p40 and p70 production. Furthermore, transfection with LMP1 expression vector into a human B lymphoma cell line, Daudi, led to p40 production with nuclear factor (NF)-kappaB activation. These results suggest that transformation of primary B cells with EBV induces IL-12 expression potentially through LMP1 expression. Copyright 1998 Academic Press.\n"
],
"offsets": [
[
0,
1106
]
]
}
] | [
{
"id": "PMID-9837745_T1",
"type": "Protein",
"text": [
"p40"
],
"offsets": [
[
533,
536
]
],
"normalized": []
},
{
"id": "PMID-9837745_T2",
"type": "Protein",
"text": [
"latent membrane protein 1"
],
"offsets": [
[
608,
633
]
],
"normalized": []
},
{
"id": "PMID-9837745_T3",
"type": "Protein",
"text": [
"LMP1"
],
"offsets": [
[
635,
639
]
],
"normalized": []
},
{
"id": "PMID-9837745_T4",
"type": "Protein",
"text": [
"p40"
],
"offsets": [
[
673,
676
]
],
"normalized": []
},
{
"id": "PMID-9837745_T5",
"type": "Protein",
"text": [
"p35"
],
"offsets": [
[
681,
684
]
],
"normalized": []
},
{
"id": "PMID-9837745_T6",
"type": "Protein",
"text": [
"p40"
],
"offsets": [
[
757,
760
]
],
"normalized": []
},
{
"id": "PMID-9837745_T7",
"type": "Protein",
"text": [
"LMP1"
],
"offsets": [
[
812,
816
]
],
"normalized": []
},
{
"id": "PMID-9837745_T8",
"type": "Protein",
"text": [
"p40"
],
"offsets": [
[
884,
887
]
],
"normalized": []
},
{
"id": "PMID-9837745_T9",
"type": "Protein",
"text": [
"LMP1"
],
"offsets": [
[
1058,
1062
]
],
"normalized": []
}
] | [] | [] | [] |
145 | PMID-7594468 | [
{
"id": "PMID-7594468__text",
"type": "abstract",
"text": [
"Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)-dependent signal transduction pathways. \nThe Ca(2+)-dependent phosphatase calcineurin, a target of FK506 and CsA, synergizes with PKC-induced activation of nuclear factor (NF)-kappa B in T cell lines. We have investigated whether this synergy is present in other cell types and the mechanism(s) by which these two pathways lead to NF-kappa B activation. While this synergy is present in other cell types, in the monocytic cell line U937 calcineurin is also sufficient to activate NF-kappa B. Having previously shown that Ca(2+)- and PKC-dependent pathways synergize by accelerating the degradation of IkB alpha, we focused on the regulation of IkB alpha phosphorylation. While PKC-dependent pathways sequentially result in the phosphorylation and in an incomplete degradation of IkB alpha in T cell lines, co-activation of Ca(2+)-dependent pathways accelerates the rate of IkB alpha phosphorylation and results in its complete degradation. Activation of Ca(2+)-dependent pathways alone do not result in the phosphorylation and/or degradation of IkB alpha in Jurkat T or in U937 cells. Treatment of T cells with the selective PKC inhibitor GF109203X abrogates the PMA-induced IkB alpha phosphorylation/degradation irrespective of activation of Ca(2+)-dependent pathways, but not the phosphorylation and degradation of IkB alpha induced by TNF-alpha, a PKC-independent stimulus. Contrary to the interaction with PKC, Ca(2+)-dependent pathways synergize with TNF-alpha not at the level of IkB alpha phosphorylation, but at the level of its degradation. These results indicate that Ca(2+)-dependent pathways, including the phosphatase calcineurin, participate in the regulation of NF-kappa B in a cell specific fashion and synergize with PKC-dependent and -independent pathways at the level of IkB alpha phosphorylation and degradation.\n"
],
"offsets": [
[
0,
1892
]
]
}
] | [
{
"id": "PMID-7594468_T1",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
14,
23
]
],
"normalized": []
},
{
"id": "PMID-7594468_T2",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
660,
669
]
],
"normalized": []
},
{
"id": "PMID-7594468_T3",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
703,
712
]
],
"normalized": []
},
{
"id": "PMID-7594468_T4",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
838,
847
]
],
"normalized": []
},
{
"id": "PMID-7594468_T5",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
932,
941
]
],
"normalized": []
},
{
"id": "PMID-7594468_T6",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
1104,
1113
]
],
"normalized": []
},
{
"id": "PMID-7594468_T7",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
1234,
1243
]
],
"normalized": []
},
{
"id": "PMID-7594468_T8",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
1376,
1385
]
],
"normalized": []
},
{
"id": "PMID-7594468_T9",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1397,
1406
]
],
"normalized": []
},
{
"id": "PMID-7594468_T10",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1515,
1524
]
],
"normalized": []
},
{
"id": "PMID-7594468_T11",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
1545,
1554
]
],
"normalized": []
},
{
"id": "PMID-7594468_T12",
"type": "Protein",
"text": [
"IkB alpha"
],
"offsets": [
[
1849,
1858
]
],
"normalized": []
}
] | [] | [] | [] |
146 | PMID-10202024 | [
{
"id": "PMID-10202024__text",
"type": "abstract",
"text": [
"Human cytomegalovirus binding to human monocytes induces immunoregulatory gene expression. \nTo continue our investigation of the cellular events that occur following human CMV (HCMV) infection, we focused on the regulation of cellular activation following viral binding to human monocytes. First, we showed that viral binding induced a number of immunoregulatory genes (IL-1beta, A20, NF-kappaB-p105/p50, and IkappaBalpha) in unactivated monocytes and that neutralizing Abs to the major HCMV glycoproteins, gB (UL55) and gH (UL75), inhibited the induction of these genes. Next, we demonstrated that these viral ligands directly up-regulated monocyte gene expression upon their binding to their appropriate cellular receptors. We then investigated if HCMV binding also resulted in the translation and secretion of cytokines. Our results showed that HCMV binding to monocytes resulted in the production and release of IL-1beta protein. Because these induced gene products have NF-kappaB sites in their promoter regions, we next examined whether there was an up-regulation of nuclear NF-kappaB levels. These experiments showed that, in fact, NF-kappaB was translocated to the nucleus following viral binding or purified viral ligand binding. Changes in IkappaBalpha levels correlated with the changes in NF-kappaB translocation. Lastly, we demonstrated that p38 kinase activity played a central role in IL-1beta production and that it was rapidly up-regulated following infection. These results support our hypothesis that HCMV initiates a signal transduction pathway that leads to monocyte activation and pinpoints a potential mechanism whereby HCMV infection of monocytes can result in profound pathogenesis, especially in chronic inflammatory-type conditions.\n"
],
"offsets": [
[
0,
1760
]
]
}
] | [
{
"id": "PMID-10202024_T1",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
370,
378
]
],
"normalized": []
},
{
"id": "PMID-10202024_T2",
"type": "Protein",
"text": [
"A20"
],
"offsets": [
[
380,
383
]
],
"normalized": []
},
{
"id": "PMID-10202024_T3",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
395,
399
]
],
"normalized": []
},
{
"id": "PMID-10202024_T4",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
400,
403
]
],
"normalized": []
},
{
"id": "PMID-10202024_T5",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
409,
421
]
],
"normalized": []
},
{
"id": "PMID-10202024_T6",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
916,
924
]
],
"normalized": []
},
{
"id": "PMID-10202024_T7",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
1250,
1262
]
],
"normalized": []
},
{
"id": "PMID-10202024_T8",
"type": "Protein",
"text": [
"IL-1beta"
],
"offsets": [
[
1400,
1408
]
],
"normalized": []
}
] | [] | [] | [] |
147 | PMID-8573121 | [
{
"id": "PMID-8573121__text",
"type": "abstract",
"text": [
"Inhibition of NF-kappa B activation in human T-cell lines by anetholdithiolthione. \nNuclear factor (NF)-kappa B is a redox sensitive cytosolic transcription factor. Redox regulation of NF-kappa B has been implicated in the activation of the human immuno-deficiency virus (HIV). Therefore, inhibition of NF-kappa B activation may be an effective strategy for acquired immunodeficiency syndrome therapy. Anetholdithiolthione (ADT, 5-[p-methoxyphenyl]-3H-1,2-dithiol-3-thione) is an antioxidant which has been used to protect against acetaminophen- and CCl4-induced hepatotoxicity, lipid peroxidation, radiation injury, and also has been used clinically as an anti-choleretic agent. The present study examined the effect of ADT pretreatment on NF-kappa B activation in response to a variety of stimuli such as H2O2, phorbol myristate acetate (PMA) or tumor necrosis factor alpha (TNF alpha). PMA and TNF alpha induced activation of (NF)-kappa B in human Jurkat T-cells was partially inhibited by ADT (0.1 mM) pretreatment. ADT (0.1 mM) also inhibited H2O2 induced activation of the transcription factor in the peroxide sensitive human Wurzburg T-cells. Furthermore, ADT treated Wurzburg cells had significantly higher glutathione levels as compared with untreated cells. H2O2 induced lipid peroxidation in Wurzburg cells was remarkably inhibited by ADT pretreatment. ADT, a pro-glutathione antioxidant, was observed to be capable of modulating NF-kappa B activation.\n"
],
"offsets": [
[
0,
1464
]
]
}
] | [
{
"id": "PMID-8573121_T1",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
848,
875
]
],
"normalized": []
},
{
"id": "PMID-8573121_T2",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
877,
886
]
],
"normalized": []
},
{
"id": "PMID-8573121_T3",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
897,
906
]
],
"normalized": []
}
] | [] | [] | [] |
148 | PMID-10229841 | [
{
"id": "PMID-10229841__text",
"type": "abstract",
"text": [
"Signaling through the lymphotoxin-beta receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-alpha. \nThe level of ongoing HIV-1 replication within an individual is critical to HIV-1 pathogenesis. Among host immune factors, the cytokine TNF-alpha has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems. Here, we demonstrate that signaling through the TNF receptor family member, the lymphotoxin-beta (LT-beta) receptor (LT-betaR), also regulates HIV-1 replication. Furthermore, HIV-1 replication is cooperatively stimulated when the distinct LT-betaR and TNF receptor systems are simultaneously engaged by their specific ligands. Moreover, in a physiological coculture cellular assay system, we show that membrane-bound TNF-alpha and LT-alpha1beta2 act virtually identically to their soluble forms in the regulation of HIV-1 replication. Thus, cosignaling via the LT-beta and TNF-alpha receptors is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in monocytes. Intriguingly, surface expression of LT-alpha1beta2 is up-regulated on a T cell line acutely infected with HIV-1, suggesting a positive feedback loop between HIV-1 infection, LT-alpha1beta2 expression, and HIV-1 replication. Given the critical role that LT-alpha1beta2 plays in lymphoid architecture, we speculate that LT-alpha1beta2 may be involved in HIV-associated abnormalities of the lymphoid organs.\n"
],
"offsets": [
[
0,
1519
]
]
}
] | [
{
"id": "PMID-10229841_T1",
"type": "Protein",
"text": [
"lymphotoxin-beta receptor"
],
"offsets": [
[
22,
47
]
],
"normalized": []
},
{
"id": "PMID-10229841_T2",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
133,
142
]
],
"normalized": []
},
{
"id": "PMID-10229841_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
280,
289
]
],
"normalized": []
},
{
"id": "PMID-10229841_T4",
"type": "Protein",
"text": [
"lymphotoxin-beta (LT-beta) receptor"
],
"offsets": [
[
472,
507
]
],
"normalized": []
},
{
"id": "PMID-10229841_T5",
"type": "Protein",
"text": [
"LT-betaR"
],
"offsets": [
[
509,
517
]
],
"normalized": []
},
{
"id": "PMID-10229841_T6",
"type": "Protein",
"text": [
"LT-betaR"
],
"offsets": [
[
631,
639
]
],
"normalized": []
},
{
"id": "PMID-10229841_T7",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
809,
818
]
],
"normalized": []
},
{
"id": "PMID-10229841_T8",
"type": "Protein",
"text": [
"LT-beta"
],
"offsets": [
[
953,
960
]
],
"normalized": []
},
{
"id": "PMID-10229841_T9",
"type": "Protein",
"text": [
"TNF-alpha receptors"
],
"offsets": [
[
965,
984
]
],
"normalized": []
}
] | [] | [] | [] |
149 | PMID-7843230 | [
{
"id": "PMID-7843230__text",
"type": "abstract",
"text": [
"Biphasic control of nuclear factor-kappa B activation by the T cell receptor complex: role of tumor necrosis factor alpha. \nThe regulation of nuclear factor (NF)-kappa B activation by the T cell receptor (TcR)/CD3 complex in primary human T cells has been studied at various times after activation. Only p50 NF-kappa B protein bound the kappa B element of interleukin-2 receptor (IL-2R) alpha chain promoter on resting T cells. However, immediately after TcR/CD3 cross-linking (after approximately 1 h; immediate) binding of p50.p65 heterodimers was observed. p50.c-rel heterodimers were also detected bound to this sequence at early time points (7-16 h; early), and both remained active at later time points (40 h; late) after activation. This regulation takes place mainly at the level of nuclear translocation of p65 and c-rel, at immediate and early time points. Activation also induced c-rel and p105/p50 mRNA synthesis, but not p65 mRNA whose expression was constitutive. Interestingly, all those early and late events, but not the immediate ones, were inhibited by a neutralizing anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody. Similarly, cycloheximide prevented the p65 and c-rel translocation and consequent formation of active binding heterodimers, at early and late times. Cyclosporin A impaired not only early and late, but also immediate events; however, addition of TNF-alpha prevented all inhibition. These results indicate that the regulation of NF-kappa B activation during T cell activation by TcR/CD3 signals is biphasic: TcR/CD3 triggers its immediate translocation, which is transient if no TNF-alpha is present. TNF-alpha, therefore, emerges as the main factor responsible for a second phase of NF-kappa B regulation, controlling both translocation of p65 and c-rel, and new mRNA synthesis for c-rel and p105/p50.\n"
],
"offsets": [
[
0,
1854
]
]
}
] | [
{
"id": "PMID-7843230_T1",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
94,
121
]
],
"normalized": []
},
{
"id": "PMID-7843230_T2",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
304,
307
]
],
"normalized": []
},
{
"id": "PMID-7843230_T3",
"type": "Protein",
"text": [
"interleukin-2 receptor (IL-2R) alpha chain"
],
"offsets": [
[
356,
398
]
],
"normalized": []
},
{
"id": "PMID-7843230_T4",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
525,
528
]
],
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"id": "PMID-7843230_T14",
"type": "Protein",
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"tumor necrosis factor alpha"
],
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"id": "PMID-7843230_T15",
"type": "Protein",
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"TNF-alpha"
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"type": "Protein",
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"p65"
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"p50"
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1849,
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}
] | [] | [] | [] |
150 | PMID-8015553 | [
{
"id": "PMID-8015553__text",
"type": "abstract",
"text": [
"Nonpituitary human prolactin gene transcription is independent of Pit-1 and differentially controlled in lymphocytes and in endometrial stroma. \nExpression of the human PRL (hPRL) gene in extrapituitary sites such as the uterus (decidualized endometrial stroma and myometrium) and cells of the hematopoietic lineage is directed by an alternative promoter which is located approximately 6 kilobases (kb) upstream of the pituitary-specific start site. In order to delineate the tissue-specific mechanisms governing the control of nonpituitary PRL gene expression, we have cloned and sequenced 3 kb 5'-flanking DNA of the upstream decidual/lymphoid (dPRL) promoter. Based on sequence homology we identified two binding motifs for Pit-1 and seven half-sites for glucocorticoid receptor/progesterone receptor (PR) binding. We focused our studies on the role of Pit-1 and of PR as potential transcriptional regulators, since the POU domain protein Pit-1 is essential in the control of pituitary PRL expression, and progesterone induces decidual transformation of the endometrial stroma, a differentiation process during which the decidual PRL gene is activated. We demonstrate in a variety of cell types, including lymphocytes and endometrial stroma, that Pit-1 is not involved in the regulation of dPRL promoter/reporter gene constructs carrying 3 kb 5'-flanking DNA. Our experiments also show that activated PR does not confer direct transcriptional control on the dPRL promoter. When we compared the activity of the transfected dPRL promoter in PRL-secreting and nonsecreting lymphoid cells, we found that the 3 kb 5'-flanking region of the dPRL promoter did not contain elements restricting expression to only those lymphocytes that produce PRL but allowed expression of fusion reporter genes irrespective of the status of the endogenous PRL gene. This was in sharp contrast to endometrial cells where 3 kb 5'-flanking DNA conferred strong transcriptional activation on the dPRL promoter in decidualized endometrial stromal cells actively secreting PRL, but did not allow transcription in undifferentiated non-PRL-secreting endometrial stromal cells. Activation of the dPRL promoter construct in these undifferentiated cells could however be induced by the addition of cAMP, in the absence of progesterone, suggesting that a signal transduced through the cAMP signaling pathway is a primary inducer of decidual PRL gene expression.\n"
],
"offsets": [
[
0,
2430
]
]
}
] | [
{
"id": "PMID-8015553_T1",
"type": "Protein",
"text": [
"prolactin"
],
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[
19,
28
]
],
"normalized": []
},
{
"id": "PMID-8015553_T2",
"type": "Protein",
"text": [
"Pit-1"
],
"offsets": [
[
66,
71
]
],
"normalized": []
},
{
"id": "PMID-8015553_T3",
"type": "Protein",
"text": [
"PRL"
],
"offsets": [
[
169,
172
]
],
"normalized": []
},
{
"id": "PMID-8015553_T4",
"type": "Protein",
"text": [
"hPRL"
],
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[
174,
178
]
],
"normalized": []
},
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"id": "PMID-8015553_T5",
"type": "Protein",
"text": [
"PRL"
],
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541,
544
]
],
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},
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"id": "PMID-8015553_T6",
"type": "Protein",
"text": [
"dPRL"
],
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[
647,
651
]
],
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},
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"id": "PMID-8015553_T7",
"type": "Protein",
"text": [
"Pit-1"
],
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[
727,
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]
],
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},
{
"id": "PMID-8015553_T8",
"type": "Protein",
"text": [
"glucocorticoid receptor"
],
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[
758,
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]
],
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},
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"id": "PMID-8015553_T9",
"type": "Protein",
"text": [
"progesterone receptor"
],
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782,
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]
],
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},
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"id": "PMID-8015553_T10",
"type": "Protein",
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"PR"
],
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805,
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]
],
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},
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"id": "PMID-8015553_T11",
"type": "Protein",
"text": [
"Pit-1"
],
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856,
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]
],
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},
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"id": "PMID-8015553_T12",
"type": "Protein",
"text": [
"PR"
],
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[
869,
871
]
],
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},
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"id": "PMID-8015553_T13",
"type": "Protein",
"text": [
"Pit-1"
],
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942,
947
]
],
"normalized": []
},
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"id": "PMID-8015553_T14",
"type": "Protein",
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"PRL"
],
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989,
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]
],
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},
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"id": "PMID-8015553_T15",
"type": "Protein",
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"PRL"
],
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1133,
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]
],
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},
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"id": "PMID-8015553_T16",
"type": "Protein",
"text": [
"Pit-1"
],
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1250,
1255
]
],
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},
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"id": "PMID-8015553_T17",
"type": "Protein",
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"dPRL"
],
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1293,
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]
],
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},
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"id": "PMID-8015553_T18",
"type": "Protein",
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"PR"
],
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]
],
"normalized": []
},
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"id": "PMID-8015553_T19",
"type": "Protein",
"text": [
"dPRL"
],
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1461,
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]
],
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},
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"id": "PMID-8015553_T20",
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"dPRL"
],
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1525,
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]
],
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},
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"id": "PMID-8015553_T21",
"type": "Protein",
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"PRL"
],
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1542,
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]
],
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},
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"id": "PMID-8015553_T22",
"type": "Protein",
"text": [
"PRL"
],
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[
1739,
1742
]
],
"normalized": []
},
{
"id": "PMID-8015553_T23",
"type": "Protein",
"text": [
"PRL"
],
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[
1836,
1839
]
],
"normalized": []
},
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"id": "PMID-8015553_T24",
"type": "Protein",
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"dPRL"
],
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1972,
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]
],
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},
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"id": "PMID-8015553_T25",
"type": "Protein",
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"PRL"
],
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]
],
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},
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"id": "PMID-8015553_T26",
"type": "Protein",
"text": [
"PRL"
],
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]
],
"normalized": []
},
{
"id": "PMID-8015553_T27",
"type": "Protein",
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"dPRL"
],
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]
],
"normalized": []
},
{
"id": "PMID-8015553_T28",
"type": "Protein",
"text": [
"PRL"
],
"offsets": [
[
2409,
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]
],
"normalized": []
}
] | [] | [] | [] |
152 | PMID-8773576 | [
{
"id": "PMID-8773576__text",
"type": "abstract",
"text": [
"The role of early growth response gene 1 (egr-1) in regulation of the immune response. \nThe induction of immediate early genes in cells of the immune system is critical to determining the ultimate outcome of exposure to antigen. The importance of many of these genes relates to the role their transcription factor products play in dictating patterns of expression of downstream, function-related genes. Evidence from several systems indicates that the immediate early gene, egr-1 may be of particular importance in the immune system. Recently, the egr-1 promoter has been shown to be highly responsive to the diverse biochemical signals generated by antigen and cytokines in cells of the immune system. Furthermore, an important role for egr-1 in determining the differentiation pathway of myeloid cell precursors has been recently elaborated. Finally, potential targets of regulation by the zinc-finger transcription factor encoded by egr-1 include the interleukin-2, CD44, ICAM-1, and tumor necrosis factor genes. The role of egr-1 in regulation of the immune response will be discussed in the context of these recent studies.\n"
],
"offsets": [
[
0,
1129
]
]
}
] | [
{
"id": "PMID-8773576_T1",
"type": "Protein",
"text": [
"early growth response gene 1"
],
"offsets": [
[
12,
40
]
],
"normalized": []
},
{
"id": "PMID-8773576_T2",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
42,
47
]
],
"normalized": []
},
{
"id": "PMID-8773576_T3",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
474,
479
]
],
"normalized": []
},
{
"id": "PMID-8773576_T4",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
548,
553
]
],
"normalized": []
},
{
"id": "PMID-8773576_T5",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
738,
743
]
],
"normalized": []
},
{
"id": "PMID-8773576_T6",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
936,
941
]
],
"normalized": []
},
{
"id": "PMID-8773576_T7",
"type": "Protein",
"text": [
"interleukin-2"
],
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[
954,
967
]
],
"normalized": []
},
{
"id": "PMID-8773576_T8",
"type": "Protein",
"text": [
"CD44"
],
"offsets": [
[
969,
973
]
],
"normalized": []
},
{
"id": "PMID-8773576_T9",
"type": "Protein",
"text": [
"ICAM-1"
],
"offsets": [
[
975,
981
]
],
"normalized": []
},
{
"id": "PMID-8773576_T10",
"type": "Protein",
"text": [
"tumor necrosis factor"
],
"offsets": [
[
987,
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]
],
"normalized": []
},
{
"id": "PMID-8773576_T11",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
1028,
1033
]
],
"normalized": []
}
] | [] | [] | [] |
153 | PMID-1945879 | [
{
"id": "PMID-1945879__text",
"type": "abstract",
"text": [
"One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter. \nThe inducible, T cell-specific enhancers of murine and human Interleukin 2 (Il-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif. When cloned in multiple copies this so-called TCEd (distal T cell element) acts as an inducible proto-enhancer element in E14 T lymphoma cells, but not in HeLa cells. In extracts of induced, Il-2 secreting El4 cells three individual protein factors bind to TCEd DNA. The binding of the most prominent factor, named TCF-1 (T cell factor 1), is correlated with the proto-enhancer activity of TCEd. TCF-1 consists of two polypeptides of about 50 kD and 105 kD; the former seems to be related to the 50 kD polypeptide of NF-kB. Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA. The conversion of the TCEd to a 'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the 'converted' TCEd motifs in HeLa cells. Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and HeLa cells. These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the Il-2 gene.\n"
],
"offsets": [
[
0,
1477
]
]
}
] | [
{
"id": "PMID-1945879_T1",
"type": "Protein",
"text": [
"interleukin 2"
],
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[
107,
120
]
],
"normalized": []
},
{
"id": "PMID-1945879_T2",
"type": "Protein",
"text": [
"Interleukin 2"
],
"offsets": [
[
193,
206
]
],
"normalized": []
},
{
"id": "PMID-1945879_T3",
"type": "Protein",
"text": [
"Il-2"
],
"offsets": [
[
208,
212
]
],
"normalized": []
},
{
"id": "PMID-1945879_T4",
"type": "Protein",
"text": [
"Il-2"
],
"offsets": [
[
495,
499
]
],
"normalized": []
},
{
"id": "PMID-1945879_T5",
"type": "Protein",
"text": [
"TCF-1"
],
"offsets": [
[
619,
624
]
],
"normalized": []
},
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"id": "PMID-1945879_T6",
"type": "Protein",
"text": [
"T cell factor 1"
],
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[
626,
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]
],
"normalized": []
},
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"id": "PMID-1945879_T7",
"type": "Protein",
"text": [
"TCF-1"
],
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700,
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]
],
"normalized": []
},
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"id": "PMID-1945879_T8",
"type": "Protein",
"text": [
"TCF-1"
],
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[
881,
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],
"normalized": []
},
{
"id": "PMID-1945879_T9",
"type": "Protein",
"text": [
"Il-2"
],
"offsets": [
[
1466,
1470
]
],
"normalized": []
}
] | [] | [] | [] |
159 | PMID-10438731 | [
{
"id": "PMID-10438731__text",
"type": "abstract",
"text": [
"C/EBPbeta and GATA-1 synergistically regulate activity of the eosinophil granule major basic protein promoter: implication for C/EBPbeta activity in eosinophil gene expression. \nEosinophil granule major basic protein (MBP) is expressed exclusively in eosinophils and basophils in hematopoietic cells. In our previous study, we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP (CCAAT/enhancer-binding protein) consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the cell line HT93A, which is capable of differentiating towards both the eosinophil and neutrophil lineages in response to retinoic acid (RA), C/EBPalpha mRNA expression decreased significantly concomitant with eosinophilic and neutrophilic differentiation, whereas C/EBPbeta expression was markedly increased. Electrophoretic mobility shift assays (EMSAs) showed that recombinant C/EBPbeta protein could bind to the potential C/EBP-binding site (bp -90 to -82) in the MBP promoter. Furthermore, we have demonstrated that both C/EBPbeta and GATA-1 can bind simultaneously to the C/EBP- and GATA-binding sites in the MBP promoter. To determine the functionality of both the C/EBP- and GATA- binding sites, we analyzed whether C/EBPbeta and GATA-1 can stimulate the MBP promoter in the C/EBPbeta and GATA-1 negative Jurkat T-cell line. Cotransfection with C/EBPbeta and GATA-1 expression vectors produced a 5-fold increase compared with cotransfection with the C/EBPbeta or GATA-1 expression vectors individually. In addition, GST pull-down experiments demonstrated a physical interaction between human GATA-1 and C/EBPbeta. Expression of FOG (riend ATA), which binds to GATA-1 and acts as a cofactor for GATA-binding proteins, decreased transactivation activity of GATA-1 for the MBP promoter in a dose-dependent manner. Our results provide the first evidence that both GATA-1 and C/EBPbeta synergistically transactivate the promoter of an eosinophil-specific granule protein gene and that FOG may act as a negative cofactor for the eosinophil lineage, unlike its positively regulatory function for the erythroid and megakaryocyte lineages.\n"
],
"offsets": [
[
0,
2283
]
]
}
] | [
{
"id": "PMID-10438731_T1",
"type": "Protein",
"text": [
"C/EBPbeta"
],
"offsets": [
[
0,
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]
],
"normalized": []
},
{
"id": "PMID-10438731_T2",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
14,
20
]
],
"normalized": []
},
{
"id": "PMID-10438731_T3",
"type": "Protein",
"text": [
"eosinophil granule major basic protein"
],
"offsets": [
[
62,
100
]
],
"normalized": []
},
{
"id": "PMID-10438731_T4",
"type": "Protein",
"text": [
"C/EBPbeta"
],
"offsets": [
[
127,
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]
],
"normalized": []
},
{
"id": "PMID-10438731_T5",
"type": "Protein",
"text": [
"Eosinophil granule major basic protein"
],
"offsets": [
[
178,
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]
],
"normalized": []
},
{
"id": "PMID-10438731_T6",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
218,
221
]
],
"normalized": []
},
{
"id": "PMID-10438731_T7",
"type": "Protein",
"text": [
"GATA-1"
],
"offsets": [
[
377,
383
]
],
"normalized": []
},
{
"id": "PMID-10438731_T8",
"type": "Protein",
"text": [
"GATA-2"
],
"offsets": [
[
419,
425
]
],
"normalized": []
},
{
"id": "PMID-10438731_T9",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
429,
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]
],
"normalized": []
},
{
"id": "PMID-10438731_T10",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
477,
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]
],
"normalized": []
},
{
"id": "PMID-10438731_T11",
"type": "Protein",
"text": [
"MBP"
],
"offsets": [
[
629,
632
]
],
"normalized": []
},
{
"id": "PMID-10438731_T12",
"type": "Protein",
"text": [
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786,
796
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"id": "PMID-10438731_T13",
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"C/EBPbeta"
],
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909,
918
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"id": "PMID-10438731_T14",
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1024,
1033
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"id": "PMID-10438731_T15",
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1112,
1115
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1170,
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1184,
1190
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1259,
1262
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"id": "PMID-10438731_T19",
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1368,
1377
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"id": "PMID-10438731_T20",
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1382,
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1407,
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"id": "PMID-10438731_T22",
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1427,
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1497,
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"C/EBPbeta"
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1602,
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"GATA-1"
],
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1615,
1621
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"id": "PMID-10438731_T28",
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1744,
1750
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],
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"id": "PMID-10438731_T29",
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"C/EBPbeta"
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[
1755,
1764
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],
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"type": "Protein",
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1812,
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"id": "PMID-10438731_T31",
"type": "Protein",
"text": [
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1907,
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],
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},
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"id": "PMID-10438731_T32",
"type": "Protein",
"text": [
"MBP"
],
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1922,
1925
]
],
"normalized": []
},
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"id": "PMID-10438731_T33",
"type": "Protein",
"text": [
"GATA-1"
],
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2012,
2018
]
],
"normalized": []
},
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"id": "PMID-10438731_T34",
"type": "Protein",
"text": [
"C/EBPbeta"
],
"offsets": [
[
2023,
2032
]
],
"normalized": []
}
] | [] | [] | [] |
160 | PMID-9312192 | [
{
"id": "PMID-9312192__text",
"type": "abstract",
"text": [
"Evidence that calcineurin is rate-limiting for primary human lymphocyte activation. \nCyclosporine (CsA) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways. In vitro, CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin (CN). In clinical use, CsA treatment inhibits 50-75% of CN activity in circulating leukocytes. We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation. In CsA-treated leukocytes stimulated by calcium ionophore, the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested: dephosphorylation of nuclear factor of activated T cell proteins, nuclear DNA binding, activation of a transfected reporter gene construct, IFN-gamma and IL-2 mRNA accumulation, and IFN-gamma production. Furthermore, the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-gamma production in the allogeneic mixed lymphocyte cultures. These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes. Thus, the reduction of CN activity observed in CsA-treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation, and accounts for the immunosuppression observed.\n"
],
"offsets": [
[
0,
1473
]
]
}
] | [
{
"id": "PMID-9312192_T1",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
908,
917
]
],
"normalized": []
},
{
"id": "PMID-9312192_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
922,
926
]
],
"normalized": []
},
{
"id": "PMID-9312192_T3",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
950,
959
]
],
"normalized": []
},
{
"id": "PMID-9312192_T4",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
1092,
1101
]
],
"normalized": []
}
] | [] | [] | [] |
161 | PMID-9649186 | [
{
"id": "PMID-9649186__text",
"type": "abstract",
"text": [
"Oxidative stress suppresses transcription factor activities in stimulated lymphocytes. \nEffects of oxidative stress on stimulation-dependent signal transduction, leading to IL-2 expression, were studied. Purified quiescent human blood T lymphocytes were subjected to: (i) acute exposure to hydrogen peroxide; (ii) chronic exposure to hydrogen peroxide; and (iii) acute exposure to ionizing radiation. The cells were then stimulated for 6 h. DNA-binding activities (determined by the electrophoretic mobility shift assay) of three transcription factors: NFkappaB, AP-1 and NFAT, were abolished in the lymphocytes by all three modes of oxidative stress. The lymphocytes exhibited lipid peroxidation only upon exposure to the lowest level of hydrogen peroxide used (20 microM). All three modes of oxidative stress induced catalase activity in the lymphocytes. The only exception was hydrogen peroxide at 20 microM, which did not induce catalase activity. We conclude that: (i) suppression of specific transcription factor functions can potentially serve as a marker of exposure to oxidative stress and its effects on human lymphocytes; (ii) lipid peroxidation is only detectable in human lymphocytes upon exposure to weak oxidative stress which does not induce catalase activity; (iii) therefore, transcription factor DNA-binding activities are more sensitive to oxidative stress than lipid peroxidation.\n"
],
"offsets": [
[
0,
1402
]
]
}
] | [
{
"id": "PMID-9649186_T1",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
173,
177
]
],
"normalized": []
}
] | [] | [] | [] |
163 | PMID-9341756 | [
{
"id": "PMID-9341756__text",
"type": "abstract",
"text": [
"Induction of endothelial cell surface adhesion molecules by tumor necrosis factor is blocked by protein tyrosine phosphatase inhibitors: role of the nuclear transcription factor NF-kappa B. \nRecent studies from our laboratory have indicated that protein tyrosine phosphatase (PTPase) inhibitors can down-modulate the tumor necrosis factor (TNF)-mediated activation of the nuclear transcription factor NF-kappa B in ML-1a, a monocytic cell line (Singh and Aggarwal, J. Biol. Chem. 1995: 270: 10631). Since TNF is one of the major inducers of various adhesion molecules in human endothelial cells and their expression is known to require the activation of NF-kappa B, we examined the effect of PTPase inhibitors on the TNF-mediated induction of intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and endothelial leukocyte adhesion molecule (ELAM)-1. Like ML-1a, human dermal microvessel endothelial cells (MVEC) treated with TNF rapidly activated (within 30 min) NF-kappa B; this effect was completely abolished by co-treatment with phenylarsine oxide (PAO), a specific inhibitor of PTPase. The induction of ICAM-1, VCAM-1, and ELAM-1 by TNF in MVEC occurred within 6 h and was also completely down-regulated by PAO in a dose-dependent manner. PAO was found to be effective even when added 3 h after TNF, suggesting a rapid mode of action of this inhibitor. Besides PAO, other inhibitors of PTPase, including pervanadate and diamide, also blocked TNF-dependent NF-kappa B activation and induction of all the three adhesion proteins. Consistent with these results, the attachment of monocytes to MVEC was also blocked by the PTPase inhibitors. Thus, overall, our results demonstrate that a PTPase is involved either directly or indirectly in the pathway leading to the induction of endothelial cell adhesion molecules by TNF. Because of their role in cell adhesion, PTPase may provide a novel target of drug development for treatment of inflammation, atherogenesis, and tumor metastasis.\n"
],
"offsets": [
[
0,
2017
]
]
}
] | [
{
"id": "PMID-9341756_T1",
"type": "Protein",
"text": [
"intracellular adhesion molecule (ICAM)-1"
],
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[
743,
783
]
],
"normalized": []
},
{
"id": "PMID-9341756_T2",
"type": "Protein",
"text": [
"vascular cell adhesion molecule (VCAM)-1"
],
"offsets": [
[
785,
825
]
],
"normalized": []
},
{
"id": "PMID-9341756_T3",
"type": "Protein",
"text": [
"endothelial leukocyte adhesion molecule (ELAM)-1"
],
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[
830,
878
]
],
"normalized": []
},
{
"id": "PMID-9341756_T4",
"type": "Protein",
"text": [
"ICAM-1"
],
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[
1138,
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"normalized": []
},
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"id": "PMID-9341756_T5",
"type": "Protein",
"text": [
"VCAM-1"
],
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1146,
1152
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},
{
"id": "PMID-9341756_T6",
"type": "Protein",
"text": [
"ELAM-1"
],
"offsets": [
[
1158,
1164
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],
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}
] | [] | [] | [] |
164 | PMID-2023633 | [
{
"id": "PMID-2023633__text",
"type": "abstract",
"text": [
"HIV enhancer activity perpetuated by NF-kappa B induction on infection of monocytes [see comments] \nPermissiveness to replication of human immunodeficiency virus (HIV) differs in T lymphocytes and macrophages. In T cells, HIV transcription is poorly detected in vivo. Cloned, normal T lymphocytes show very little, if any, basal activity of the HIV enhancer and low nuclear expression of NF-kappa B, a potent transcriptional activator of the HIV enhancer. In contrast, fixed tissue macrophages express detectable HIV proteins, indicating permanent virus transcription. One explanation for the perpetuation of virus infection in macrophages could be sustained nuclear NF-kappa B expression. However, the U937 monocytic cell line, which is fully permissive to HIV replication, is known to express only low levels of nuclear NF-kappa B. We show here that chronic HIV infection results in both induction of a nuclear factor with antigenic properties indistinguishable from those of NF-kappa B and permanently increased HIV enhancer activity. This phenomenon, which is independent of tumour necrosis factor, is associated with HIV replication, and is thus likely to explain at least in part the perpetuation of HIV infection in monocytes.\n"
],
"offsets": [
[
0,
1234
]
]
}
] | [] | [] | [] | [] |
168 | PMID-10082134 | [
{
"id": "PMID-10082134__text",
"type": "abstract",
"text": [
"Cobalt chloride-induced signaling in endothelium leading to the augmented adherence of sickle red blood cells and transendothelial migration of monocyte-like HL-60 cells is blocked by PAF-receptor antagonist. \nIn response to hypoxia, sickle red blood cells (SS RBC) and leukocytes exhibit increased adherence to the vascular endothelium, while diapedesis of leukocytes through the blood vessel increases. However, the cellular signaling pathway(s) caused by hypoxia is poorly understood. We utilized CoCl2 as a mimetic molecule for hypoxia to study cellular signaling pathways. We found that in human umbilical vein endothelial cells (HUVEC), CoCl2 at 2 mM concentration induced the surface expression of a subset of CAMs (VCAM-1) and activation of transcription factor NF-kappaB in the nuclear extracts of HUVEC. Furthermore, CoCl2 also caused time-dependent tyrosine phosphorylation of mitogen-activated protein (MAP) kinase isoform ERK2 without significantly affecting ERK1, indicating ERK2 is the preferred substrate for upstream kinase of the MAPK pathway. Inhibitors of MAP kinase (PD98059) or platelet-activating factor (PAF)- receptor antagonist (CV3988) inhibited the CoCl2-induced NF-kappaB activation and VCAM-1 expression. Augmented expression of VCAM-1 led to increased SS RBC adhesion, inhibitable by a VCAM-1 antibody. Additionally, CoCl2 caused a two- to threefold increase in the rate of transendothelial migration of monocyte-like HL-60 cells and a twentyfold increase in phosphorylation of platelet endothelial cell adhesion molecules (PECAM-1). The transendothelial migration of monocytes was inhibited by an antibody to PECAM-1. Both phosphorylation of PECAM-1 and transendothelial migration of monocytes in response to CoCl2 were inhibited by protein kinase inhibitor (GF109203X) and augmented by protein phosphatase inhibitor (Calyculin A). Our data suggests that CoCl2-induced cellular signals directing increased expression of VCAM-1 in HUVEC involve downstream activation of MAP kinase and NF-kappaB, while the phosphorylation of PECAM-1 occurs as a result of activation of PKC. We conclude that PAF-receptor antagonist inhibits the CoCl2- or hypoxia-induced increase in the adhesion of SS RBC, PECAM-1 phosphorylation, and the concomitant transendothelial migration of monocytes.\n"
],
"offsets": [
[
0,
2307
]
]
}
] | [
{
"id": "PMID-10082134_T1",
"type": "Protein",
"text": [
"PAF-receptor"
],
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[
184,
196
]
],
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},
{
"id": "PMID-10082134_T2",
"type": "Protein",
"text": [
"VCAM-1"
],
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[
723,
729
]
],
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},
{
"id": "PMID-10082134_T3",
"type": "Protein",
"text": [
"ERK2"
],
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935,
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]
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},
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"id": "PMID-10082134_T4",
"type": "Protein",
"text": [
"ERK1"
],
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972,
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"id": "PMID-10082134_T5",
"type": "Protein",
"text": [
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],
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989,
993
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},
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"id": "PMID-10082134_T6",
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1216,
1222
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},
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"id": "PMID-10082134_T7",
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],
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1259,
1265
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],
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},
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"id": "PMID-10082134_T8",
"type": "Protein",
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"VCAM-1"
],
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1317,
1323
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],
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},
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"id": "PMID-10082134_T9",
"type": "Protein",
"text": [
"PECAM-1"
],
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[
1555,
1562
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],
"normalized": []
},
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"id": "PMID-10082134_T10",
"type": "Protein",
"text": [
"PECAM-1"
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1641,
1648
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],
"normalized": []
},
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"id": "PMID-10082134_T11",
"type": "Protein",
"text": [
"PECAM-1"
],
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[
1674,
1681
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},
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"id": "PMID-10082134_T12",
"type": "Protein",
"text": [
"VCAM-1"
],
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1952,
1958
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},
{
"id": "PMID-10082134_T13",
"type": "Protein",
"text": [
"PECAM-1"
],
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[
2056,
2063
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],
"normalized": []
},
{
"id": "PMID-10082134_T14",
"type": "Protein",
"text": [
"PECAM-1"
],
"offsets": [
[
2221,
2228
]
],
"normalized": []
}
] | [] | [] | [] |
170 | PMID-7565732 | [
{
"id": "PMID-7565732__text",
"type": "abstract",
"text": [
"Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor. \nT-lymphocyte proliferation is suppressed by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D3, and is associated with a decrease in interleukin 2 (IL-2), gamma interferon, and granulocyte-macrophage colony-stimulating factor mRNA levels. We report here that 1,25(OH)2D3-mediated repression in Jurkat cells is cycloheximide resistant, suggesting that it is a direct transcriptional repressive effect on IL-2 expression by the vitamin D3 receptor (VDR). We therefore examined vitamin D3-mediated repression of activated IL-2 expression by cotransfecting Jurkat cells with IL-2 promoter/reporter constructs and a VDR overexpression vector and by DNA binding. We delineated an element conferring both DNA binding by the receptor in vitro and 1,25(OH)2D3-mediated repression in vivo to a short 40-bp region encompassing an important positive regulatory element, NF-AT-1, which is bound by a T-cell-specific transcription factor, NFATp, as well as by AP-1. VDR DNA-binding mutants were unable to either bind to this element in vitro or repress in vivo; the VDR DNA-binding domain alone, however, bound the element but also could not repress IL-2 expression. These results indicate that DNA binding by VDR is necessary but not sufficient to mediate IL-2 repression. By combining partially purified proteins in vitro, we observed the loss of the bound NFATp/AP-1-DNA complex upon inclusion of VDR or VDR-retinoid X receptor. Order of addition and off-rate experiments indicate that the VDR-retinoid X receptor heterodimer blocks NFATp/AP-1 complex formation and then stably associates with the NF-AT-1 element. This direct inhibition by a nuclear hormone receptor of transcriptional activators of the IL-2 gene may provide a mechanistic explanation of how vitamin derivatives can act as potent immunosuppressive agents.\n"
],
"offsets": [
[
0,
1988
]
]
}
] | [
{
"id": "PMID-7565732_T1",
"type": "Protein",
"text": [
"interleukin-2"
],
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[
34,
47
]
],
"normalized": []
},
{
"id": "PMID-7565732_T2",
"type": "Protein",
"text": [
"NFATp"
],
"offsets": [
[
89,
94
]
],
"normalized": []
},
{
"id": "PMID-7565732_T3",
"type": "Protein",
"text": [
"interleukin 2"
],
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[
308,
321
]
],
"normalized": []
},
{
"id": "PMID-7565732_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
323,
327
]
],
"normalized": []
},
{
"id": "PMID-7565732_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
578,
582
]
],
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},
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"id": "PMID-7565732_T6",
"type": "Protein",
"text": [
"vitamin D3 receptor"
],
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[
601,
620
]
],
"normalized": []
},
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"id": "PMID-7565732_T7",
"type": "Protein",
"text": [
"VDR"
],
"offsets": [
[
622,
625
]
],
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},
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"id": "PMID-7565732_T8",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
694,
698
]
],
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},
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"id": "PMID-7565732_T9",
"type": "Protein",
"text": [
"IL-2"
],
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[
746,
750
]
],
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},
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"id": "PMID-7565732_T10",
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"text": [
"VDR"
],
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[
786,
789
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],
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},
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"id": "PMID-7565732_T11",
"type": "Protein",
"text": [
"NF-AT-1"
],
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[
1033,
1040
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],
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},
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"id": "PMID-7565732_T12",
"type": "Protein",
"text": [
"NFATp"
],
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[
1100,
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},
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"id": "PMID-7565732_T13",
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"VDR"
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1127,
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},
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"id": "PMID-7565732_T14",
"type": "Protein",
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"VDR"
],
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[
1227,
1230
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},
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"id": "PMID-7565732_T15",
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"IL-2"
],
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[
1311,
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},
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"id": "PMID-7565732_T16",
"type": "Protein",
"text": [
"VDR"
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[
1371,
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},
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"id": "PMID-7565732_T17",
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"text": [
"IL-2"
],
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1418,
1422
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},
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"id": "PMID-7565732_T18",
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"text": [
"NFATp"
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[
1520,
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],
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},
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"id": "PMID-7565732_T19",
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"VDR"
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[
1561,
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},
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"id": "PMID-7565732_T20",
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"VDR"
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1568,
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},
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"id": "PMID-7565732_T21",
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"text": [
"VDR"
],
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[
1654,
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],
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},
{
"id": "PMID-7565732_T22",
"type": "Protein",
"text": [
"NFATp"
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1697,
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},
{
"id": "PMID-7565732_T23",
"type": "Protein",
"text": [
"NF-AT-1"
],
"offsets": [
[
1762,
1769
]
],
"normalized": []
},
{
"id": "PMID-7565732_T24",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1869,
1873
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],
"normalized": []
}
] | [] | [] | [] |
172 | PMID-8018558 | [
{
"id": "PMID-8018558__text",
"type": "abstract",
"text": [
"Activation of early growth response 1 gene transcription and pp90rsk during induction of monocytic differentiation. \nThe present work has studied mechanisms responsible for induction of early growth response 1 (EGR-1) gene expression during monocytic differentiation of U-937 myeloid leukemia cells. Differentiation of U-937 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of the serine/threonine protein kinase C, was associated with transcriptional activation of EGR-1 promoter-reporter constructs. The EGR-1 promoter contains six CC(A/T)6GG (CArG) motifs. The two 5'-most distal CArG sequences conferred TPA inducibility. In contrast, there was little effect of TPA on EGR-1 transcription in a TPA-resistant U-937 cell variant, designated TUR. Treatment of both U-937 and TUR cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases 1 and 2A, was associated with induction of monocytic differentiation and EGR-1 transcription through the 5'-most CArG element. Since these findings supported the involvement of serine/threonine protein phosphorylation in the regulation of EGR-1 expression, we studied activation of the 40S ribosomal protein S6 serine/threonine kinases, pp70S6K and pp90rsk. Although both kinases participate in regulating cell growth, there was no detectable activation of pp70S6K during TPA- or okadaic acid-induced monocytic differentiation. Moreover, rapamycin, an inhibitor of pp70S6K activation, had no effect on induction of EGR-1 expression. In contrast, analysis of pp90rsk activity by phosphorylation of a peptide derived from S6 protein demonstrated stimulation of this kinase in TPA-treated U-937, and not TUR, cells. Okadaic acid treatment of both cell types was associated with activation of pp90rsk.\n"
],
"offsets": [
[
0,
1776
]
]
}
] | [
{
"id": "PMID-8018558_T1",
"type": "Protein",
"text": [
"early growth response 1"
],
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[
14,
37
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"normalized": []
},
{
"id": "PMID-8018558_T2",
"type": "Protein",
"text": [
"early growth response 1"
],
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[
186,
209
]
],
"normalized": []
},
{
"id": "PMID-8018558_T3",
"type": "Protein",
"text": [
"EGR-1"
],
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[
211,
216
]
],
"normalized": []
},
{
"id": "PMID-8018558_T4",
"type": "Protein",
"text": [
"EGR-1"
],
"offsets": [
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485,
490
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],
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},
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"id": "PMID-8018558_T5",
"type": "Protein",
"text": [
"EGR-1"
],
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[
525,
530
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},
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"id": "PMID-8018558_T6",
"type": "Protein",
"text": [
"EGR-1"
],
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692,
697
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],
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"id": "PMID-8018558_T7",
"type": "Protein",
"text": [
"EGR-1"
],
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951,
956
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],
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"id": "PMID-8018558_T8",
"type": "Protein",
"text": [
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],
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1117,
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],
"normalized": []
},
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"id": "PMID-8018558_T9",
"type": "Protein",
"text": [
"EGR-1"
],
"offsets": [
[
1493,
1498
]
],
"normalized": []
}
] | [] | [] | [] |
176 | PMID-2234062 | [
{
"id": "PMID-2234062__text",
"type": "abstract",
"text": [
"Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs. \nWe have cloned and characterized a mitogen-inducible gene isolated from human T cells that predicts a protein of 968 amino acids. The amino-terminal domain has regions homologous to the oncogene rel and to the developmentally important gene dorsal of Drosophila. The carboxy-terminal domain contains repeat structures found in a variety of proteins that are involved in cell-cycle control of yeast and in tissue differentiation in Drosophila and Ceanorhabditis elegans, as well as in the putative human oncogene bcl-3 and in the ankyrin protein. A truncated form of the product of this gene translated in vitro is a DNA-binding protein which interacts specifically with the kappa B binding site found in many inducible genes, including the enhancer in human immunodeficiency virus. This gene is yet another in a growing list of important regulatory molecules whose expression is transcriptionally induced upon cellular activation.\n"
],
"offsets": [
[
0,
1067
]
]
}
] | [] | [] | [] | [] |
178 | PMID-8934542 | [
{
"id": "PMID-8934542__text",
"type": "abstract",
"text": [
"Cell specific expression of human Bruton's agammaglobulinemia tyrosine kinase gene (Btk) is regulated by Sp1- and Spi-1/PU.1-family members. \nBruton's agammaglobulinemia tyrosine kinase (Btk) is a cytoplasmic tyrosine kinase involved in the human disease X-linked agammaglobulinemia (XLA). The gene is expressed in all hematopoietic cells with the exception of T-cells and plasma cells. For this expression pattern the first 280 bp upstream of the major transcriptional start site seems to be sufficient. In vitro footprinting analysis within this part of the promoter revealed two Sp1 binding sites as well as a PU-box. The transcription factor Spi-1/PU.1 as well as the closely related factor Spi-B bound to the PU-box in B-cells. In the erythroleukemia cell line K562, due to the absence of Spi-B, only PU.1 bound to the Btk promoter. Mutation of either site reduced the expression in transient transfection experiments. However, mutation of the PU box had no effect in the T-cell line Jurkat, where none of the Spi-1 family members is expressed. In addition Spi-B as well as PU.1 were able to transactivate Btk expression. In fetal liver of PU.1-/- mice, which lack lymphoid and myeloid cells, expression of Btk was reduced two- to threefold but not abolished. Collectively this study shows that expression of the Btk gene is regulated by the combined action of Sp1- and PU.1-family members.\n"
],
"offsets": [
[
0,
1396
]
]
}
] | [
{
"id": "PMID-8934542_T1",
"type": "Protein",
"text": [
"Bruton's agammaglobulinemia tyrosine kinase"
],
"offsets": [
[
34,
77
]
],
"normalized": []
},
{
"id": "PMID-8934542_T2",
"type": "Protein",
"text": [
"Btk"
],
"offsets": [
[
84,
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]
],
"normalized": []
},
{
"id": "PMID-8934542_T3",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
105,
108
]
],
"normalized": []
},
{
"id": "PMID-8934542_T4",
"type": "Protein",
"text": [
"Spi-1"
],
"offsets": [
[
114,
119
]
],
"normalized": []
},
{
"id": "PMID-8934542_T5",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
120,
124
]
],
"normalized": []
},
{
"id": "PMID-8934542_T6",
"type": "Protein",
"text": [
"Bruton's agammaglobulinemia tyrosine kinase"
],
"offsets": [
[
142,
185
]
],
"normalized": []
},
{
"id": "PMID-8934542_T7",
"type": "Protein",
"text": [
"Btk"
],
"offsets": [
[
187,
190
]
],
"normalized": []
},
{
"id": "PMID-8934542_T8",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
582,
585
]
],
"normalized": []
},
{
"id": "PMID-8934542_T9",
"type": "Protein",
"text": [
"Spi-1"
],
"offsets": [
[
646,
651
]
],
"normalized": []
},
{
"id": "PMID-8934542_T10",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
652,
656
]
],
"normalized": []
},
{
"id": "PMID-8934542_T11",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
695,
700
]
],
"normalized": []
},
{
"id": "PMID-8934542_T12",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
794,
799
]
],
"normalized": []
},
{
"id": "PMID-8934542_T13",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
806,
810
]
],
"normalized": []
},
{
"id": "PMID-8934542_T14",
"type": "Protein",
"text": [
"Btk"
],
"offsets": [
[
824,
827
]
],
"normalized": []
},
{
"id": "PMID-8934542_T15",
"type": "Protein",
"text": [
"Spi-1"
],
"offsets": [
[
1015,
1020
]
],
"normalized": []
},
{
"id": "PMID-8934542_T16",
"type": "Protein",
"text": [
"Spi-B"
],
"offsets": [
[
1062,
1067
]
],
"normalized": []
},
{
"id": "PMID-8934542_T17",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1079,
1083
]
],
"normalized": []
},
{
"id": "PMID-8934542_T18",
"type": "Protein",
"text": [
"Btk"
],
"offsets": [
[
1111,
1114
]
],
"normalized": []
},
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"id": "PMID-8934542_T19",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1145,
1149
]
],
"normalized": []
},
{
"id": "PMID-8934542_T20",
"type": "Protein",
"text": [
"Btk"
],
"offsets": [
[
1212,
1215
]
],
"normalized": []
},
{
"id": "PMID-8934542_T21",
"type": "Protein",
"text": [
"Btk"
],
"offsets": [
[
1318,
1321
]
],
"normalized": []
},
{
"id": "PMID-8934542_T22",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1366,
1369
]
],
"normalized": []
},
{
"id": "PMID-8934542_T23",
"type": "Protein",
"text": [
"PU.1"
],
"offsets": [
[
1375,
1379
]
],
"normalized": []
}
] | [] | [] | [] |
179 | PMID-10358756 | [
{
"id": "PMID-10358756__text",
"type": "abstract",
"text": [
"Transcriptional regulation of T lymphocyte development and function. \nThe development and function of T lymphocytes are regulated tightly by signal transduction pathways that include specific cell-surface receptors, intracellular signaling molecules, and nuclear transcription factors. Since 1988, several families of functionally important T cell transcription factors have been identified. These include the Ikaros, LKLF, and GATA3 zinc-finger proteins; the Ets, CREB/ATF, and NF-kappa B/Rel/NFAT transcription factors; the Stat proteins; and HMG box transcription factors such as LEF1, TCF1, and Sox4. In this review, we summarize our current understanding of the transcriptional regulation of T cell development and function with particular emphasis on the results of recent gene targeting and transgenic experiments. In addition to increasing our understanding of the molecular pathways that regulate T cell development and function, these results have suggested novel targets for genetic and pharmacological manipulation of T cell immunity.\n"
],
"offsets": [
[
0,
1047
]
]
}
] | [
{
"id": "PMID-10358756_T1",
"type": "Protein",
"text": [
"Ikaros"
],
"offsets": [
[
410,
416
]
],
"normalized": []
},
{
"id": "PMID-10358756_T2",
"type": "Protein",
"text": [
"LKLF"
],
"offsets": [
[
418,
422
]
],
"normalized": []
},
{
"id": "PMID-10358756_T3",
"type": "Protein",
"text": [
"GATA3"
],
"offsets": [
[
428,
433
]
],
"normalized": []
},
{
"id": "PMID-10358756_T4",
"type": "Protein",
"text": [
"CREB"
],
"offsets": [
[
465,
469
]
],
"normalized": []
},
{
"id": "PMID-10358756_T5",
"type": "Protein",
"text": [
"ATF"
],
"offsets": [
[
470,
473
]
],
"normalized": []
},
{
"id": "PMID-10358756_T6",
"type": "Protein",
"text": [
"LEF1"
],
"offsets": [
[
583,
587
]
],
"normalized": []
},
{
"id": "PMID-10358756_T7",
"type": "Protein",
"text": [
"TCF1"
],
"offsets": [
[
589,
593
]
],
"normalized": []
},
{
"id": "PMID-10358756_T8",
"type": "Protein",
"text": [
"Sox4"
],
"offsets": [
[
599,
603
]
],
"normalized": []
}
] | [] | [] | [] |
180 | PMID-1386962 | [
{
"id": "PMID-1386962__text",
"type": "abstract",
"text": [
"The development of functionally responsive T cells. \nThe work reviewed in this article separates T cell development into four phases. First is an expansion phase prior to TCR rearrangement, which appears to be correlated with programming of at least some response genes for inducibility. This phase can occur to some extent outside of the thymus. However, the profound T cell deficit of nude mice indicates that the thymus is by far the most potent site for inducing the expansion per se, even if other sites can induce some response acquisition. Second is a controlled phase of TCR gene rearrangement. The details of the regulatory mechanism that selects particular loci for rearrangement are still not known. It seems that the rearrangement of the TCR gamma loci in the gamma delta lineage may not always take place at a developmental stage strictly equivalent to the rearrangement of TCR beta in the alpha beta lineage, and it is not clear just how early the two lineages diverge. In the TCR alpha beta lineage, however, the final gene rearrangement events are accompanied by rapid proliferation and an interruption in cellular response gene inducibility. The loss of conventional responsiveness is probably caused by alterations at the level of signaling, and may be a manifestation of the physiological state that is a precondition for selection. Third is the complex process of selection. Whereas peripheral T cells can undergo forms of positive selection (by antigen-driven clonal expansion) and negative selection (by abortive stimulation leading to anergy or death), neither is exactly the same phenomenon that occurs in the thymic cortex. Negative selection in the cortex appears to be a suicidal inversion of antigen responsiveness: instead of turning on IL-2 expression, the activated cell destroys its own chromatin. The genes that need to be induced for this response are not yet identified, but it is unquestionably a form of activation. It is interesting that in humans and rats, cortical thymocytes undergoing negative selection can still induce IL-2R alpha expression and even be rescued in vitro, if exogenous IL-2 is provided. Perhaps murine thymocytes are denied this form of rescue because they shut off IL-2R beta chain expression at an earlier stage or because they may be uncommonly Bcl-2 deficient (cf. Sentman et al., 1991; Strasser et al., 1991). Even so, medullary thymocytes remain at least partially susceptible to negative selection even as they continue to mature .\n"
],
"offsets": [
[
0,
2499
]
]
}
] | [
{
"id": "PMID-1386962_T1",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1766,
1770
]
],
"normalized": []
},
{
"id": "PMID-1386962_T2",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
2063,
2074
]
],
"normalized": []
},
{
"id": "PMID-1386962_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
2129,
2133
]
],
"normalized": []
},
{
"id": "PMID-1386962_T4",
"type": "Protein",
"text": [
"IL-2R beta chain"
],
"offsets": [
[
2226,
2242
]
],
"normalized": []
},
{
"id": "PMID-1386962_T5",
"type": "Protein",
"text": [
"Bcl-2"
],
"offsets": [
[
2308,
2313
]
],
"normalized": []
}
] | [] | [] | [] |
183 | PMID-8054477 | [
{
"id": "PMID-8054477__text",
"type": "abstract",
"text": [
"Positive and negative regulation of IL-2 gene expression: role of multiple regulatory sites. \nInterleukin 2 (IL-2) is an important lymphokine required in the process of T cell activation, proliferation, clonal expansion and differentiation. The IL-2 gene displays both T cell specific and inducible expression: it is only expressed in CD4+ T cells after antigenic or mitogenic stimulation. Several cis-acting regulatory sites are required for induction of the IL-2 gene after stimulation. In this study, we have analysed the function of these cis-acting regulatory sites in the context of the native IL-2 enhancer and promoter sequence. The results of this study suggest that the NFAT (-276 to -261), the distal octamer (-256 to -248) and the proximal octamer (-75 to -66) sites not only act as enhancers of IL-2 gene transcription in the presence of cellular stimulation, but also have a silencing effect on IL-2 gene expression in resting cells. Two other sites display disparate effects on IL-2 gene expression in different T leukemia cell lines: the distal purine box (-291 to -277) and the proximal purine box sites (-145 to -128). Finally, the AP-1 (-186 to -176) and the kappa B sites (-206 to -195) respond to different cellular activation in EL4 cells. The AP-1 site mediated the response to PMA stimulation while the kappa B site responded to IL-1 stimulation. These data suggest that the regulation of IL-2 gene expression is a complex process and multiple cis-acting regulatory sites interact to exert different effects in T cells representative of alternative stages of differentiation.\n"
],
"offsets": [
[
0,
1600
]
]
}
] | [
{
"id": "PMID-8054477_T1",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
36,
40
]
],
"normalized": []
},
{
"id": "PMID-8054477_T2",
"type": "Protein",
"text": [
"Interleukin 2"
],
"offsets": [
[
94,
107
]
],
"normalized": []
},
{
"id": "PMID-8054477_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
109,
113
]
],
"normalized": []
},
{
"id": "PMID-8054477_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
245,
249
]
],
"normalized": []
},
{
"id": "PMID-8054477_T5",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
335,
338
]
],
"normalized": []
},
{
"id": "PMID-8054477_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
460,
464
]
],
"normalized": []
},
{
"id": "PMID-8054477_T7",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
600,
604
]
],
"normalized": []
},
{
"id": "PMID-8054477_T8",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
808,
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]
],
"normalized": []
},
{
"id": "PMID-8054477_T9",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
909,
913
]
],
"normalized": []
},
{
"id": "PMID-8054477_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
993,
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]
],
"normalized": []
},
{
"id": "PMID-8054477_T11",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1413,
1417
]
],
"normalized": []
}
] | [] | [] | [] |
187 | PMID-9834092 | [
{
"id": "PMID-9834092__text",
"type": "abstract",
"text": [
"Regulation of NF-kappa B, AP-1, NFAT, and STAT1 nuclear import in T lymphocytes by noninvasive delivery of peptide carrying the nuclear localization sequence of NF-kappa B p50. \nActivation of T lymphocytes by Ags or cytokines results in translocation of the transcription factors NF-kappa B, AP-1, NFAT, and STAT from the cytoplasm into the nucleus. The first step in the nuclear import process is recognition of a nuclear localization sequence (NLS) within the karyophilic protein by a cytoplasmic receptor such as the importin (karyopherin)-alpha subunit. The NLSs of NF-kappa B, AP-1, and NFAT differ and the NLS of STAT1 has not yet been identified. Herein we demonstrate that the inducible nuclear import of NF-kappa B, AP-1, NFAT, and STAT1 in Jurkat T lymphocytes is significantly inhibited by a cell-permeable peptide carrying the NLS of the NF-kappa B p50 subunit. NLS peptide-mediated disruption of the nuclear import of these transcription factors results in inhibition of I kappa B alpha and IL-2 gene expression, processes dependent on NF-kappa B or the combination of NF-kappa B, AP-1, and NFAT. Further, we show that inhibitory NLS peptide interacts in vitro with a cytoplasmic NLS receptor complex comprised of the Rch1/importin (karyopherin)-beta heterodimer expressed in Jurkat T cells. Taken together, these data indicate that the inducible nuclear import of NF-kappa B, AP-1, NFAT, and STAT1 in Jurkat T cells can be regulated by NLS peptide delivered noninvasively to the cytoplasm of Jurkat T cells to target members of the importin (karyopherin)-alpha beta NLS receptor complex.\n"
],
"offsets": [
[
0,
1602
]
]
}
] | [
{
"id": "PMID-9834092_T1",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
42,
47
]
],
"normalized": []
},
{
"id": "PMID-9834092_T2",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
172,
175
]
],
"normalized": []
},
{
"id": "PMID-9834092_T3",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
741,
746
]
],
"normalized": []
},
{
"id": "PMID-9834092_T4",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
861,
864
]
],
"normalized": []
},
{
"id": "PMID-9834092_T5",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
984,
999
]
],
"normalized": []
},
{
"id": "PMID-9834092_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1004,
1008
]
],
"normalized": []
},
{
"id": "PMID-9834092_T7",
"type": "Protein",
"text": [
"Rch1"
],
"offsets": [
[
1231,
1235
]
],
"normalized": []
},
{
"id": "PMID-9834092_T8",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
1406,
1411
]
],
"normalized": []
}
] | [] | [] | [] |
188 | PMID-8018594 | [
{
"id": "PMID-8018594__text",
"type": "abstract",
"text": [
"Effects of prostaglandin E2 on Th0-type human T cell clones: modulation of functions of nuclear proteins involved in cytokine production. \nThe effects of prostaglandin E2 (PGE2) on cytokine production and proliferation of the CD4+ human helper T cell clone SP-B21 were investigated. In cells stimulated with anti-CD3 mAb, PGE2 inhibited cell proliferation and the production of all the cytokines examined. Addition of rIL-2 fully restored the proliferative response and partially restored the production of IL-4 and IL-5, but not that of other cytokines. In contrast, in cells stimulated with phorbol myristate acetate (PMA)/A23187, PGE2 enhanced the production of IL-4 and IL-5, and only partially inhibited the production of other cytokines. Therefore, the effects of PGE2 vary depending on the mode of T cell activation, and the IL-4 and IL-5 are regulated differently from other cytokines. In a mobility shift assay, only the NF-kappa B (p50/p50) homodimer was observed in a complex formed with the kappa B sequence in unstimulated SP-B21 cells. When cells were stimulated with anti-CD3 mAb or PMA/A23187, a complex formation of NF-kappa B (p50/p65) heterodimer with the kappa B sequence was induced. Interestingly, PGE2 or di-butyryl (Bt2)cAMP abolished the binding of NF-kappa B (p50/p65) heterodimer to the kappa B sequence in cells stimulated with anti-CD3 mAb but not with PMA/A23187. Our results suggest that the target of PGE2 action is a component in the signal transduction pathway leading to the activation of protein kinase C. However, the inhibition of the T cell activation signals by PGE2 is selective. PGE2 enhanced the complex formation with NF-AT, AP-1 and CLE0 sequences when the cells were activated by either anti-CD3 mAb or PMA/A23187 stimulation. It seems therefore that PGE2, by elevating cAMP levels, interferes with the activation pathway for NF-kappa B but not for NF-AT, AP-1 or CLE0 binding protein.\n"
],
"offsets": [
[
0,
1932
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]
}
] | [
{
"id": "PMID-8018594_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
226,
229
]
],
"normalized": []
},
{
"id": "PMID-8018594_T2",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
507,
511
]
],
"normalized": []
},
{
"id": "PMID-8018594_T3",
"type": "Protein",
"text": [
"IL-5"
],
"offsets": [
[
516,
520
]
],
"normalized": []
},
{
"id": "PMID-8018594_T4",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
665,
669
]
],
"normalized": []
},
{
"id": "PMID-8018594_T5",
"type": "Protein",
"text": [
"IL-5"
],
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[
674,
678
]
],
"normalized": []
},
{
"id": "PMID-8018594_T6",
"type": "Protein",
"text": [
"IL-4"
],
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[
832,
836
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],
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},
{
"id": "PMID-8018594_T7",
"type": "Protein",
"text": [
"IL-5"
],
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[
841,
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],
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},
{
"id": "PMID-8018594_T8",
"type": "Protein",
"text": [
"p50"
],
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[
942,
945
]
],
"normalized": []
},
{
"id": "PMID-8018594_T9",
"type": "Protein",
"text": [
"p50"
],
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[
946,
949
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],
"normalized": []
},
{
"id": "PMID-8018594_T10",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1145,
1148
]
],
"normalized": []
},
{
"id": "PMID-8018594_T11",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1149,
1152
]
],
"normalized": []
},
{
"id": "PMID-8018594_T12",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1286,
1289
]
],
"normalized": []
},
{
"id": "PMID-8018594_T13",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1290,
1293
]
],
"normalized": []
}
] | [] | [] | [] |
189 | PMID-9933632 | [
{
"id": "PMID-9933632__text",
"type": "abstract",
"text": [
"NF-kappaB activation is a critical regulator of human granulocyte apoptosis in vitro. \nDuring beneficial inflammation, potentially tissue-damaging granulocytes undergo apoptosis before being cleared by phagocytes in a non-phlogistic manner. Here we show that the rate of constitutive apoptosis in human neutrophils and eosinophils is greatly accelerated in both a rapid and concentration-dependent manner by the fungal metabolite gliotoxin, but not by its inactive analog methylthiogliotoxin. This induction of apoptosis was abolished by the caspase inhibitor zVAD-fmk, correlated with the inhibition of nuclear factor-kappa B (NF-kappaB), and was mimicked by a cell permeable inhibitory peptide of NF-kappaB, SN-50; other NF-kappaB inhibitors, curcumin and pyrrolidine dithiocarbamate; and the proteasome inhibitor, MG-132. Gliotoxin also augmented dramatically the early (2-6 h) pro-apoptotic effects of tumor necrosis factor-alpha (TNF-alpha) in neutrophils and unmasked the ability of TNF-alpha to induce eosinophil apoptosis. In neutrophils, TNF-alpha caused a gliotoxin-inhibitable activation of an inducible form of NF-kappaB, a response that may underlie the ability of TNF-alpha to delay apoptosis at later times (12-24 h) and limit its early killing effect. Furthermore, cycloheximide displayed a similar capacity to enhance TNF-alpha induced neutrophil apoptosis even at time points when cycloheximide alone had no pro-apoptotic effect, suggesting that NF-kappaB may regulate the production of protein(s) which protect neutrophils from the cytotoxic effects of TNF-alpha. These data shed light on the biochemical and molecular mechanisms regulating human granulocyte apoptosis and, in particular, indicate that the transcription factor NF-kappaB plays a crucial role in regulating the physiological cell death pathway in granulocytes.\n"
],
"offsets": [
[
0,
1846
]
]
}
] | [
{
"id": "PMID-9933632_T1",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
906,
933
]
],
"normalized": []
},
{
"id": "PMID-9933632_T2",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
935,
944
]
],
"normalized": []
},
{
"id": "PMID-9933632_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
989,
998
]
],
"normalized": []
},
{
"id": "PMID-9933632_T4",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1047,
1056
]
],
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},
{
"id": "PMID-9933632_T5",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1178,
1187
]
],
"normalized": []
},
{
"id": "PMID-9933632_T6",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1335,
1344
]
],
"normalized": []
},
{
"id": "PMID-9933632_T7",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1572,
1581
]
],
"normalized": []
}
] | [] | [] | [] |
192 | PMID-9057086 | [
{
"id": "PMID-9057086__text",
"type": "abstract",
"text": [
"Differentiation of U-937 promonocytic cells by etoposide and ICRF-193, two antitumour DNA topoisomerase II inhibitors with different mechanisms of action. \nWe have compared the action on U-937 human promonocytic leukemia cells of two DNA topoisomerase II inhibitors, namely the epipodophyllotoxin etoposide and the bisdioxopiperazine ICRF-193. One hour pulse-treatment with 3 microM etoposide caused topoisomerase associated, primary DNA breakage, which was rapidly followed by apoptosis. By contrast, these effects were not observed upon pulse-treatment with 6 microM ICRF-193. However, continuous treatments with subcytotoxic concentrations of etoposide (0.15 microM) and ICRF-193 (0.3 microM) produced several similar effects, namely decreased cell proliferation, accumulation of cells at G2, increase in cell mass, and induction of differentiation. Under these conditions, etoposide produced a biphasic activation of protein kinase C, which consisted in an early transient activation (from hours 1 to 6) of the membrane-bound enzyme followed by a later activation (hour 48) of the total, membrane-bound and cytosolic enzyme. By contrast, ICRF-193 only provoked a late activation (from hours 72 to 96) of the total enzyme. When used at differentiation-inducing concentrations, both topoisomerase inhibitors caused a great stimulation of AP-1 binding activity, with maximum value at hour 12 in etoposide-treated cells and at hour 48 in ICRF-193-treated cells. By contrast, the binding activity of the NF-kappa(B) and EGR-1 transcription factors was little affected. It is concluded that topoisomerase II inhibitors may induce the differentiation of promonocytic cells, independently of their capacity to cause DNA strand breaks. However, there are other effects, such as the early activation of protein kinase C, which are probably derived from the production of primary DNA breakage by some anti-topoisomerase drugs.\n"
],
"offsets": [
[
0,
1920
]
]
}
] | [
{
"id": "PMID-9057086_T1",
"type": "Protein",
"text": [
"EGR-1"
],
"offsets": [
[
1519,
1524
]
],
"normalized": []
}
] | [] | [] | [] |
End of preview. Expand
in Dataset Viewer.
Dataset Card for GENIA Relation Corpus
The extraction of various relations stated to hold between biomolecular entities is one of the most frequently addressed information extraction tasks in domain studies. Typical relation extraction targets involve protein-protein interactions or gene regulatory relations. However, in the GENIA corpus, such associations involving change in the state or properties of biomolecules are captured in the event annotation.
The GENIA corpus relation annotation aims to complement the event annotation of the corpus by capturing (primarily) static relations, relations such as part-of that hold between entities without (necessarily) involving change.
Citation Information
@inproceedings{pyysalo-etal-2009-static,
title = "Static Relations: a Piece in the Biomedical Information Extraction Puzzle",
author = "Pyysalo, Sampo and
Ohta, Tomoko and
Kim, Jin-Dong and
Tsujii, Jun{'}ichi",
booktitle = "Proceedings of the {B}io{NLP} 2009 Workshop",
month = jun,
year = "2009",
address = "Boulder, Colorado",
publisher = "Association for Computational Linguistics",
url = "https://aclanthology.org/W09-1301",
pages = "1--9",
}
@article{article,
author = {Ohta, Tomoko and Pyysalo, Sampo and Kim, Jin-Dong and Tsujii, Jun'ichi},
year = {2010},
month = {10},
pages = {917-28},
title = {A reevaluation of biomedical named entity - term relations},
volume = {8},
journal = {Journal of bioinformatics and computational biology},
doi = {10.1142/S0219720010005014}
}
@MISC{Hoehndorf_applyingontology,
author = {Robert Hoehndorf and Axel-cyrille Ngonga Ngomo and Sampo Pyysalo and Tomoko Ohta and Anika Oellrich and
Dietrich Rebholz-schuhmann},
title = {Applying ontology design patterns to the implementation of relations in GENIA},
year = {}
}
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