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10358173 | 10358173 | [
{
"id": "10358173__text",
"type": "abstract",
"text": [
"IL-12 induces IFN regulating factor-1 (IRF-1) gene expression in human NK and T cells. \nIL-12 is a critical immunoregulatory cytokine that promotes cell-mediated immune responses and the differentiation of naive CD4+ cells to Th1 cells; however, relatively few IL-12 target genes have been identified. To better clarify the molecular basis of IL-12 action, we set out to characterize genes up-regulated by IL-12, first by contrasting IL-12- and IFN-alpha-inducible genes. We identified several genes up-regulated by IL-12, namely, MIP-1alpha, MIP-1beta, IL-1RA, and IFN regulatory factor-1 (IRF-1). IRF-1 is a transcription factor regulated by IFNs that is also essential for Th1 responses. We demonstrated that IL-12 directly up-regulates IRF-1 to the same extent as IFN-alpha in normal human T cells and in NK cells. We showed that IL-12 had a direct effect on IRF-1, an effect not mediated indirectly by the induction of IFN-gamma production. Furthermore, IL-2 and IL-12 synergistically induced IRF-1, whereas IFN-alpha and IL-12 did not. The participation of STAT4 in the regulation of IRF-1 was demonstrated in two ways. First, STAT4 was required for the IL-12-dependent transactivation of an IRF-1 reporter construct, and second, STAT4 binding to the IRF-1 promoter was shown using EMSA. In contrast to IL-12, no up-regulation of IRF-1 was found in IL-4-stimulated cells, and IL-4 did not block IL-12-dependent up-regulation of IRF-1. Therefore, IRF-1 may be an important contributor to IL-12 signaling, and we speculate that the defective IL-12 responses seen in IRF-1-/- mice might be attributable, in part, to the absence of this transcription factor. "
],
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{
"id": "10358173_T1",
"type": "Protein",
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],
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{
"id": "10358173_T2",
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"type": "Protein",
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{
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"type": "Protein",
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{
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"type": "Protein",
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{
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"type": "Protein",
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{
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"type": "Protein",
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{
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{
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{
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"type": "Protein",
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{
"id": "10358173_T21",
"type": "Protein",
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{
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{
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{
"id": "10358173_T25",
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"IRF-1"
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{
"id": "10358173_T39",
"type": "Entity",
"text": [
"promoter"
],
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}
] | [
{
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"type": "Positive_regulation",
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"induces"
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"role": "Theme",
"ref_id": "10358173_E2"
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{
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"expression"
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{
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},
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"up-regulated"
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"role": "Theme",
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"regulated"
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"production"
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"synergistically induced"
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"participation"
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"ref_id": "10358173_E15"
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"regulation"
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},
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"ref_id": "10358173_T18"
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}
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"role": "Theme",
"ref_id": "10358173_T20"
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},
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"block"
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},
"arguments": [
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"role": "Theme",
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}
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] | [
{
"id": "10358173_1",
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"10358173_T2"
]
},
{
"id": "10358173_2",
"entity_ids": [
"10358173_T7",
"10358173_T8"
]
}
] | [] |
7520914 | 7520914 | [
{
"id": "7520914__text",
"type": "abstract",
"text": [
"CD14-mediated translocation of nuclear factor-kappa B induced by lipopolysaccharide does not require tyrosine kinase activity. \nDuring the course of serious bacterial infections, lipopolysaccharide (LPS) is believed to interact with macrophage receptors, resulting in the generation of inflammatory mediators and systemic symptoms including hemodynamic instability and shock. CD14, a glycosylphosphatidylinositol-linked antigen, functions as an LPS signaling receptor. A critical issue concerns the mechanism by which CD14, which has no transmembrane domain, transduces its signal following LPS binding. Recently, investigators have hypothesized that CD14-mediated signaling is effected through a receptor-associated tyrosine kinase (TK), suggesting a multicomponent receptor model of LPS signaling. Wild-type Chinese hamster ovary (CHO)-K1 cells can be activated by endotoxin to release arachidonate following transfection with human CD14 (CHO/CD14). Nuclear translocation of cytosolic NF-kappa B is correlated with a number of LPS-inducible responses. We sought to determine if this pathway were present in CHO/CD14 cells and to elucidate the relationship of NF-kappa B activation to the CD14 receptor system. LPS-stimulated translocation of NF-kappa B in CHO/CD14 cells resembled the same response in the murine macrophage-like cell line RAW 264.7. Protein synthesis inhibitors and corticosteroids, which suppress arachidonate release and the synthesis of proinflammatory cytokines, had no effect on translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells, demonstrating that NF-kappa B translocation is an early event. Although TK activity was consistently observed by immunoblotting extracts from activated RAW 264.7 cells, LPS-induced phosphotyrosine residues were not observed from similarly treated CHO/CD14 cells. Furthermore, the TK inhibitors herbimycin A and genistein failed to inhibit translocation of NF-kappa B in CHO/CD14 or RAW 264.7 cells, although both of these agents inhibited LPS-induced TK activity in RAW 264.7 cells. These results imply that TK activity is not obligatory for CD14-mediated signal transduction to occur in response to LPS. "
],
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"receptor"
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"role": "Theme",
"ref_id": "7520914_T2"
}
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"binding"
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"role": "Theme",
"ref_id": "7520914_T3"
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"id": "7520914_E3",
"type": "Gene_expression",
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"transfection"
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"role": "Theme",
"ref_id": "7520914_T5"
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},
{
"id": "7520914_E4",
"type": "Positive_regulation",
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"text": [
"transfection"
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911,
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7520914_E3"
}
]
}
] | [] | [] |
2109187 | 2109187 | [
{
"id": "2109187__text",
"type": "abstract",
"text": [
"Identification of a novel factor that interacts with an immunoglobulin heavy-chain promoter and stimulates transcription in conjunction with the lymphoid cell-specific factor OTF2. \nThe tissue-specific expression of the MOPC 141 immunoglobulin heavy-chain gene was studied by using in vitro transcription. B-cell-specific transcription of this gene was dependent on the octamer element 5'-ATGCAAAG-3', located in the upstream region of this promoter and in the promoters of all other immunoglobulin heavy- and light-chain genes. The interaction of purified octamer transcription factors 1 and 2 (OTF1 and OTF2) with the MOPC 141 promoter was studied by using electrophoretic mobility shift assays and DNase I footprinting. Purified OTF1 from HeLa cells and OTF1 and OTF2 from B cells bound to identical sequences within the heavy-chain promoter. The OTF interactions we observed extended over the heptamer element 5'-CTCAGGA-3', and it seems likely that the binding of the purified factors involves cooperation between octamer and heptamer sites in this promoter. In addition to these elements, we identified a second regulatory element, the N element with the sequence 5'-GGAACCTCCCCC-3'. The N element could independently mediate low levels of transcription in both B-cell and HeLa-cell extracts, and, in conjunction with the octamer element, it can promote high levels of transcription in B-cell extracts. The N element bound a transcription factor, NTF, that is ubiquitous in cell-type distribution, and NTF was distinct from any of the previously described proteins that bind to similar sequences. Based on these results, we propose that NTF and OTF2 interactions (both with their cognate DNA elements and possibly at the protein-protein level) may be critical to B-cell-specific expression and that these interactions provide additional pathways for regulating gene expression. "
],
"offsets": [
[
0,
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]
]
}
] | [
{
"id": "2109187_T1",
"type": "Protein",
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"OTF2"
],
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175,
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]
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{
"id": "2109187_T2",
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"text": [
"octamer transcription factors 1"
],
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"text": [
"2"
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"id": "2109187_T4",
"type": "Protein",
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"OTF1"
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"type": "Protein",
"text": [
"OTF2"
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1651,
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],
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}
] | [
{
"id": "2109187_E1",
"type": "Binding",
"trigger": {
"text": [
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}
] | [] | [] |
8809111 | 8809111 | [
{
"id": "8809111__text",
"type": "abstract",
"text": [
"Characterization of the human myeloid cell nuclear differentiation antigen gene promoter. \nMNDA (myeloid cell nuclear differentiation antigen) is an interferon alpha regulated nuclear protein expressed only in cells of the human myelomonocytic lineage. To identify mechanisms responsible for this lineage-specific and interferon-regulated expression, the 5' flanking sequence of the gene has been characterized. Two interferon-stimulated response elements (ISRE) flank a multiple transcription start site region identifying MNDA as a TATA-less interferon-regulated gene. Other DNA elements present include a cluster of Myb sites, several Ets, an Ets related PU.1 site and an Sp1 site located within 600 bp of the transcription start sites. In addition, DNA methylation was revealed as one of the possible factors in establishing MNDA expression. The 5' flanking sequence has promoter activity which is elevated by interferon alpha. The findings indicate that MNDA expression is regulated by mechanisms similar to other myelomonocytic cell specific genes and genes up-regulated by interferon alpha. "
],
"offsets": [
[
0,
1098
]
]
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}
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"type": "Regulation",
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]
]
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"role": "Theme",
"ref_id": "8809111_T3"
}
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"arguments": [
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"role": "Theme",
"ref_id": "8809111_E9"
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] | [
{
"id": "8809111_1",
"entity_ids": [
"8809111_T1",
"8809111_T2"
]
}
] | [] |
9101089 | 9101089 | [
{
"id": "9101089__text",
"type": "abstract",
"text": [
"Induction of relA(p65) and I kappa B alpha subunit expression during differentiation of human peripheral blood monocytes to macrophages. \nWe evaluated the expression and DNA binding activity of nuclear factor (NF)-kappa B subunits in human peripheral blood monocytes and in monocyte-derived macrophages (MDMs). Constitutive DNA binding activity consisting of p50 homodimers was detected in nuclear extracts from both cell types. An additional complex composed of p50/RelA(p65) heterodimers appeared only in nuclear extracts from 7-day MDMs. Immunoblot analysis showed that the p50 subunit was constitutively expressed in monocytes and MDMs. In contrast, the RelA(p65) subunit was barely detectable in monocytes, but its level increased markedly in MDMs. Analysis of RelA(p65) mRNA revealed that the stability of RelA(p65) mRNA was significantly higher in MDMs, compared with monocytes. In MDMs, an upregulation of I kappa B alpha synthesis as well as the appearance of a novel M(r) 40,000 form of I kappa B alpha were also observed. These results suggest that macrophage differentiation results in the expression of active p50/RelA(p65) heterodimers with the capacity to activate target gene expression. The parallel induction of I kappa B alpha synthesis may allow for the continuous presence of a cytoplasmic reservoir of p50/RelA(p65) complexes that are readily available for inducer-mediated stimulation. "
],
"offsets": [
[
0,
1409
]
]
}
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],
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{
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"id": "9101089_T5",
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"id": "9101089_T10",
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"p65"
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"id": "9101089_T11",
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],
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}
] | [
{
"id": "9101089_E1",
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"role": "Theme",
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"expression"
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]
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"role": "Theme",
"ref_id": "9101089_T18"
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"id": "9101089_E22",
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"induction"
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"role": "Theme",
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"role": "Theme",
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"role": "Theme",
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"role": "Theme",
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"role": "Cause",
"ref_id": "9101089_E22"
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},
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"id": "9101089_E27",
"type": "Localization",
"trigger": {
"text": [
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9101089_T23"
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"role": "AtLoc",
"ref_id": "9101089_T40"
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"id": "9101089_E28",
"type": "Localization",
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"text": [
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1311,
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"role": "AtLoc",
"ref_id": "9101089_T40"
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"id": "9101089_E29",
"type": "Localization",
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"arguments": [
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"role": "Theme",
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}
] | [] | [] |
8663230 | 8663230 | [
{
"id": "8663230__text",
"type": "abstract",
"text": [
"Mapping of the transcriptional repression domain of the lymphoid-specific transcription factor oct-2A. \nThe lymphoid-specific transcription factor Oct-2a is implicated in B cell-specific transcriptional activity via the octamer motif. Structure/function analysis of various Oct-2a effector regions in the context of the GAL4 DNA-binding domain revealed that Oct-2a contains two functionally different activation domains at the N and the C termini. The transcriptional activity of both domains is strongly potentiated by interactions with distinct B cell-specific coactivators. Recently, we have identified a repression domain located within the N terminus of Oct-2a (amino acids 2-99). When this domain was transferred to a potent activator, transcription was strongly inhibited. In this study we present a deletion analysis of the N-terminal region of Oct-2a to determine the minimal repression domain. We identified a stretch of 23 amino acids, rich in serine and threonine residues, which was responsible for most of the repression activity. We show that repression is strongly dependent on the type of enhancer present in the reporter plasmid as well as on the cell line tested. The possibility that Oct-2a can act as an activator and/or a repressor may have important consequences for the function of Oct-2a in B cell differentiation and other developmental processes. "
],
"offsets": [
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0,
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]
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}
] | [
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"id": "8663230_T1",
"type": "Protein",
"text": [
"oct-2A"
],
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95,
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]
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{
"id": "8663230_T2",
"type": "Protein",
"text": [
"Oct-2a"
],
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147,
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]
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{
"id": "8663230_T3",
"type": "Protein",
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],
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274,
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]
],
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},
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"id": "8663230_T4",
"type": "Protein",
"text": [
"GAL4"
],
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320,
324
]
],
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"id": "8663230_T5",
"type": "Protein",
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"Oct-2a"
],
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358,
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]
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],
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],
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439,
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],
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}
] | [
{
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"text": [
"potentiated"
],
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505,
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"role": "Theme",
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"ref_id": "8663230_T11"
}
]
},
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"text": [
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505,
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"role": "Site",
"ref_id": "8663230_T11"
}
]
}
] | [] | [] |
2039752 | 2039752 | [
{
"id": "2039752__text",
"type": "abstract",
"text": [
"Cortivazol mediated induction of glucocorticoid receptor messenger ribonucleic acid in wild-type and dexamethasone-resistant human leukemic (CEM) cells. \nCortivazol is a phenylpyrazolo glucocorticoid of high potency and unusual structure. In both wild-type and highly dexamethasone(dex)-resistant clones of the human leukemic cell line CEM, exposure to cortivazol leads to cell death. It has been shown recently that in wild-type CEM cells but not in a dex-resistant, glucocorticoid receptor(GR)-defective clone ICR-27 TK-3, dex induces GR mRNA. To test the hypothesis that cortivazol acts in dex-resistant cells by making use of the residual GR found there, wild-type and dex-resistant clones were treated with various concentrations of cortivazol and induction of GR mRNA was studied. Cortivazol significantly induced GR mRNA in the normal CEM-C7 as well as in two classes of dex-resistant clones, although the dex-resistant clones needed at least 10 times more cortivazol than the normal cells for significant GR mRNA induction. Increased levels of GR mRNA were noticed as early as 3 h after treatment. A general correlation between induction of GR mRNA and lysis of the normal and dex-resistant cells was found. Positive induction of GR mRNA might be one of the earliest crucial steps in the lysis of normal and dex-resistant CEM cells, or might serve as a marker for the process. However, the lysis pathway in the dex-resistant cells is defective in that dex-resistant clones needed significantly more cortivazol than the normal cells for lysis of the cells. "
],
"offsets": [
[
0,
1564
]
]
}
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"id": "2039752_T1",
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],
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33,
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"id": "2039752_T2",
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],
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468,
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]
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"GR"
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"text": [
"GR"
],
"offsets": [
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1238,
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]
],
"normalized": []
}
] | [
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"text": [
"induction"
],
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20,
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]
]
},
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"ref_id": "2039752_T1"
}
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]
},
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]
},
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"role": "Theme",
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}
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},
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"levels"
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]
]
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"role": "Theme",
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}
]
}
] | [] | [] |
7565683 | 7565683 | [
{
"id": "7565683__text",
"type": "abstract",
"text": [
"N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity. \nThe proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide. In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation. Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein. (ABSTRACT TRUNCATED AT 250 WORDS) "
],
"offsets": [
[
0,
1656
]
]
}
] | [
{
"id": "7565683_T1",
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],
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51,
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]
],
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},
{
"id": "7565683_T2",
"type": "Protein",
"text": [
"I kappa B alpha"
],
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[
56,
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]
],
"normalized": []
},
{
"id": "7565683_T3",
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],
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175,
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]
],
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},
{
"id": "7565683_T4",
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"I kappa B alpha"
],
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180,
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],
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],
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"id": "7565683_T7",
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"I kappa B alpha"
],
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]
],
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"I kappa B alpha"
],
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},
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"I kappa B alpha"
],
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1348,
1363
]
],
"normalized": []
}
] | [
{
"id": "7565683_E1",
"type": "Regulation",
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"text": [
"control"
],
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28,
35
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_E2"
}
]
},
{
"id": "7565683_E2",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
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36,
47
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_T1"
}
]
},
{
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"type": "Positive_regulation",
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"text": [
"in response to"
],
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72,
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "7565683_E2"
}
]
},
{
"id": "7565683_E4",
"type": "Protein_catabolism",
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"text": [
"proteolytic degradation"
],
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125,
148
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "7565683_T3"
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]
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"in response to"
],
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196,
210
]
]
},
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"role": "Theme",
"ref_id": "7565683_E4"
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]
},
{
"id": "7565683_E6",
"type": "Gene_expression",
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"text": [
"expression"
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334,
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]
},
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"role": "Theme",
"ref_id": "7565683_T5"
}
]
},
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"type": "Protein_catabolism",
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"text": [
"degraded"
],
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502,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_T6"
}
]
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"type": "Positive_regulation",
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"text": [
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],
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]
]
},
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"role": "Theme",
"ref_id": "7565683_E7"
}
]
},
{
"id": "7565683_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"stabilizes"
],
"offsets": [
[
792,
802
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_T7"
}
]
},
{
"id": "7565683_E10",
"type": "Phosphorylation",
"trigger": {
"text": [
"hyperphosphorylated"
],
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805,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_T7"
}
]
},
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"id": "7565683_E11",
"type": "Positive_regulation",
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"text": [
"induced"
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1012,
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]
]
},
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{
"role": "Theme",
"ref_id": "7565683_E13"
}
]
},
{
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"type": "Positive_regulation",
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"text": [
"induced"
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1012,
1019
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_E14"
}
]
},
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"text": [
"phosphorylation"
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]
},
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"role": "Theme",
"ref_id": "7565683_T8"
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"degradation"
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]
},
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"role": "Theme",
"ref_id": "7565683_T8"
}
]
},
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"type": "Positive_regulation",
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"text": [
"inducible"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_E16"
}
]
},
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"type": "Phosphorylation",
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"text": [
"phosphorylation"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_T10"
}
]
},
{
"id": "7565683_E17",
"type": "Negative_regulation",
"trigger": {
"text": [
"abolish"
],
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_E19"
}
]
},
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"text": [
"induced"
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_E19"
}
]
},
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"id": "7565683_E19",
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"text": [
"degradation"
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_T10"
}
]
},
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"text": [
"abolish"
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]
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{
"role": "Theme",
"ref_id": "7565683_E23"
}
]
},
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"type": "Negative_regulation",
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"text": [
"abolish"
],
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1572,
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_E22"
}
]
},
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"type": "Positive_regulation",
"trigger": {
"text": [
"inducible"
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_E23"
}
]
},
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"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7565683_T10"
}
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}
] | [
{
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"entity_ids": [
"7565683_T1",
"7565683_T2"
]
},
{
"id": "7565683_2",
"entity_ids": [
"7565683_T3",
"7565683_T4"
]
}
] | [] |
8662666 | 8662666 | [
{
"id": "8662666__text",
"type": "abstract",
"text": [
"DNA triplex formation selectively inhibits granulocyte-macrophage colony-stimulating factor gene expression in human T cells. \nGranulocyte-macrophage colony-stimulating factor (GM-CSF) is a hemopoietic growth factor that is expressed in activated T cells, fibroblasts, macrophages, and endothelial cells. Although GM-CSF does not appear to be essential for normal hemopoiesis, overexpression of GM-CSF has been implicated in the pathogenesis of some diseases such as myeloid leukemia and chronic inflammation. An NF-kappaB/Rel binding site within the GM-CSF promoter, termed the kappaB element appears to be important for controlling expression in reporter gene assays in response to a number of stimuli in T cells. We investigated oligonucleotide-directed triple helix formation across this regulatory sequence as a potential tool to inhibit GM-CSF gene transcription. A 15-base oligonucleotide, GM3, was targeted to a purine-rich region in the GM-CSF proximal promoter, which overlaps the kappaB element. Gel mobility shift assays and DNase I footprinting demonstrated that GM3 formed a sequence-specific collinear triplex with its double-stranded DNA target. Triplex formation by GM3 blocked recombinant and nuclear NF-kappaB proteins binding to the GM-CSF element. GM3 also caused selective inhibition of the human T-cell lymphotrophic virus-1 Tax transactivator-induced luciferase activity from a reporter construct driven by the GM-CSF promoter in Jurkat T cells. Finally, GM3 greatly reduced the concentration of endogenous GM-CSF mRNA induced by different stimuli in Jurkat T cells but did not affect interleukin 3 mRNA levels in the same cells. We conclude that the kappaB element in the GM-CSF promoter plays a central role in the transcriptional activation of the endogenous GM-CSF gene. Colinear triplex formation acts as a selective transcriptional repressor of the GM-CSF gene and may have potential therapeutic application in cases of undesirable overexpression of this protein. "
],
"offsets": [
[
0,
1994
]
]
}
] | [
{
"id": "8662666_T1",
"type": "Protein",
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"granulocyte-macrophage colony-stimulating factor"
],
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[
43,
91
]
],
"normalized": []
},
{
"id": "8662666_T2",
"type": "Protein",
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"Granulocyte-macrophage colony-stimulating factor"
],
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127,
175
]
],
"normalized": []
},
{
"id": "8662666_T3",
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"GM-CSF"
],
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177,
183
]
],
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},
{
"id": "8662666_T4",
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],
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314,
320
]
],
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},
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"id": "8662666_T5",
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],
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395,
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]
],
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},
{
"id": "8662666_T6",
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],
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551,
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]
],
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},
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"GM-CSF"
],
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843,
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]
],
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},
{
"id": "8662666_T8",
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"GM-CSF"
],
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946,
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]
],
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},
{
"id": "8662666_T9",
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"text": [
"DNase I"
],
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1037,
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]
],
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},
{
"id": "8662666_T10",
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],
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]
],
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},
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"id": "8662666_T11",
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1348,
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]
],
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},
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"GM-CSF"
],
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1435,
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]
],
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},
{
"id": "8662666_T13",
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"GM-CSF"
],
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1531,
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]
],
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},
{
"id": "8662666_T14",
"type": "Protein",
"text": [
"interleukin 3"
],
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1609,
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]
],
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},
{
"id": "8662666_T15",
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],
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1697,
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]
],
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},
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"id": "8662666_T16",
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],
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1786,
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]
],
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},
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"GM-CSF"
],
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1879,
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]
],
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},
{
"id": "8662666_T26",
"type": "Entity",
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"proximal promoter"
],
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953,
970
]
],
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},
{
"id": "8662666_T30",
"type": "Entity",
"text": [
"kappaB element"
],
"offsets": [
[
1675,
1689
]
],
"normalized": []
}
] | [
{
"id": "8662666_E1",
"type": "Negative_regulation",
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"text": [
"inhibits"
],
"offsets": [
[
34,
42
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_E2"
}
]
},
{
"id": "8662666_E2",
"type": "Gene_expression",
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"expression"
],
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97,
107
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T1"
}
]
},
{
"id": "8662666_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
224,
233
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T3"
}
]
},
{
"id": "8662666_E4",
"type": "Positive_regulation",
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"text": [
"overexpression"
],
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377,
391
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8662666_E5"
}
]
},
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"type": "Gene_expression",
"trigger": {
"text": [
"overexpression"
],
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377,
391
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T5"
}
]
},
{
"id": "8662666_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
835,
842
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_E7"
}
]
},
{
"id": "8662666_E7",
"type": "Transcription",
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"text": [
"transcription"
],
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855,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T7"
}
]
},
{
"id": "8662666_E8",
"type": "Binding",
"trigger": {
"text": [
"targeted"
],
"offsets": [
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T8"
},
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"role": "Site",
"ref_id": "8662666_T26"
}
]
},
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"id": "8662666_E9",
"type": "Negative_regulation",
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"text": [
"reduced"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_E10"
}
]
},
{
"id": "8662666_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1543,
1550
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T13"
}
]
},
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"id": "8662666_E11",
"type": "Regulation",
"trigger": {
"text": [
"affect"
],
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1602,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T14"
}
]
},
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"id": "8662666_E12",
"type": "Positive_regulation",
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"text": [
"central role"
],
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]
]
},
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{
"role": "Theme",
"ref_id": "8662666_E13"
},
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"role": "Cause",
"ref_id": "8662666_T15"
},
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"role": "CSite",
"ref_id": "8662666_T30"
}
]
},
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"id": "8662666_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"transcriptional activation"
],
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1741,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T16"
}
]
},
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"id": "8662666_E14",
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"trigger": {
"text": [
"transcriptional repressor"
],
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1846,
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]
]
},
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{
"role": "Theme",
"ref_id": "8662666_T17"
}
]
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"type": "Positive_regulation",
"trigger": {
"text": [
"overexpression"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_E16"
}
]
},
{
"id": "8662666_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
1962,
1976
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8662666_T17"
}
]
}
] | [
{
"id": "8662666_1",
"entity_ids": [
"8662666_T2",
"8662666_T3"
]
}
] | [] |
10202937 | 10202937 | [
{
"id": "10202937__text",
"type": "abstract",
"text": [
"Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling. \nFludarabine is a nucleoside analog used in the treatment of hematologic malignancies that can induce severe and prolonged immunosuppression. Although it can be incorporated into the DNA of dividing cells, fludarabine is also a potent inhibitor of cells with a low growth fraction, thus it must have other mechanisms of action. STAT1, which is activated in response to many lymphocyte-activating cytokines including the interferons, is essential for cell-mediated immunity, as the absence of this protein is associated with prominent defects in the ability to control viral infections. Here we show that fludarabine, but not the immunosuppressant cyclosporine A, inhibits the cytokine-induced activation of STAT1 and STAT1-dependent gene transcription in normal resting or activated lymphocytes. Fludarabine caused a specific depletion of STAT1 protein (and mRNA) but not of other STATs. This loss of STAT1 was also seen in cells from patients treated with fludarabine in vivo. Brief exposure to fludarabine led to a sustained loss of STAT1, analogous to the prolonged period of immunosuppression induced by exposure to the drug in vivo. Thus, STAT1 may be a useful target in the development of new immunosuppressive and antineoplastic agents. "
],
"offsets": [
[
0,
1332
]
]
}
] | [
{
"id": "10202937_T1",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
71,
76
]
],
"normalized": []
},
{
"id": "10202937_T2",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
416,
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]
],
"normalized": []
},
{
"id": "10202937_T3",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
795,
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]
],
"normalized": []
},
{
"id": "10202937_T4",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
805,
810
]
],
"normalized": []
},
{
"id": "10202937_T5",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
927,
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]
],
"normalized": []
},
{
"id": "10202937_T6",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
989,
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]
],
"normalized": []
},
{
"id": "10202937_T7",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
1123,
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]
],
"normalized": []
},
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"id": "10202937_T8",
"type": "Protein",
"text": [
"STAT1"
],
"offsets": [
[
1232,
1237
]
],
"normalized": []
}
] | [
{
"id": "10202937_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
432,
441
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202937_T2"
}
]
},
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"id": "10202937_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"absence"
],
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[
569,
576
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202937_T2"
}
]
},
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"id": "10202937_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibits"
],
"offsets": [
[
751,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202937_E4"
}
]
},
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"id": "10202937_E4",
"type": "Positive_regulation",
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"text": [
"activation"
],
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[
781,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202937_T3"
}
]
},
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"id": "10202937_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"caused"
],
"offsets": [
[
896,
902
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202937_E6"
}
]
},
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"id": "10202937_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"depletion"
],
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[
914,
923
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202937_T5"
}
]
},
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"id": "10202937_E7",
"type": "Negative_regulation",
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"text": [
"loss"
],
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[
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "10202937_T6"
}
]
},
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"id": "10202937_E8",
"type": "Positive_regulation",
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"text": [
"led"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202937_E9"
}
]
},
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"id": "10202937_E9",
"type": "Negative_regulation",
"trigger": {
"text": [
"loss"
],
"offsets": [
[
1115,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10202937_T7"
}
]
}
] | [] | [] |
7859290 | 7859290 | [
{
"id": "7859290__text",
"type": "abstract",
"text": [
"OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins. \nRecent biochemical and genetic studies indicate that in addition to the octamer-binding proteins Oct-1 and Oct-2, other B cell components are required for lymphoid-restricted, octamer site-mediated immunoglobulin gene promoter activity. Using a genetic screen in yeast, we have isolated B cell-derived cDNAs encoding Oct-binding factor 1 (OBF-1), a novel protein that specifically associates with Oct-1 and Oct-2. Biochemical studies demonstrate that OBF-1 has no intrinsic DNA-binding activity and recognizes the POU domains of Oct-1 and Oct-2, but not those of Oct-4 and Oct-6. The OBF-1 mRNA is expressed in a highly cell-specific manner, being most abundant in B cells and essentially absent in most of the other cells or tissues tested. Furthermore, expression of OBF-1 in HeLa cells selectively stimulates the activity of a natural immunoglobulin promoter in an octamer site-dependent manner. Thus, OBF-1 has all the properties expected for a B cell-specific transcriptional coactivator protein. "
],
"offsets": [
[
0,
1146
]
]
}
] | [
{
"id": "7859290_T1",
"type": "Protein",
"text": [
"OBF-1"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "7859290_T2",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
241,
246
]
],
"normalized": []
},
{
"id": "7859290_T3",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
251,
256
]
],
"normalized": []
},
{
"id": "7859290_T4",
"type": "Protein",
"text": [
"Oct-binding factor 1"
],
"offsets": [
[
461,
481
]
],
"normalized": []
},
{
"id": "7859290_T5",
"type": "Protein",
"text": [
"OBF-1"
],
"offsets": [
[
483,
488
]
],
"normalized": []
},
{
"id": "7859290_T6",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
541,
546
]
],
"normalized": []
},
{
"id": "7859290_T7",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
551,
556
]
],
"normalized": []
},
{
"id": "7859290_T8",
"type": "Protein",
"text": [
"OBF-1"
],
"offsets": [
[
595,
600
]
],
"normalized": []
},
{
"id": "7859290_T9",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
673,
678
]
],
"normalized": []
},
{
"id": "7859290_T10",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
683,
688
]
],
"normalized": []
},
{
"id": "7859290_T11",
"type": "Protein",
"text": [
"Oct-4"
],
"offsets": [
[
707,
712
]
],
"normalized": []
},
{
"id": "7859290_T12",
"type": "Protein",
"text": [
"Oct-6"
],
"offsets": [
[
717,
722
]
],
"normalized": []
},
{
"id": "7859290_T13",
"type": "Protein",
"text": [
"OBF-1"
],
"offsets": [
[
728,
733
]
],
"normalized": []
},
{
"id": "7859290_T14",
"type": "Protein",
"text": [
"OBF-1"
],
"offsets": [
[
913,
918
]
],
"normalized": []
},
{
"id": "7859290_T15",
"type": "Protein",
"text": [
"OBF-1"
],
"offsets": [
[
1049,
1054
]
],
"normalized": []
},
{
"id": "7859290_T20",
"type": "Entity",
"text": [
"POU domains"
],
"offsets": [
[
658,
669
]
],
"normalized": []
}
] | [
{
"id": "7859290_E1",
"type": "Binding",
"trigger": {
"text": [
"association"
],
"offsets": [
[
100,
111
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7859290_T1"
}
]
},
{
"id": "7859290_E2",
"type": "Binding",
"trigger": {
"text": [
"associates"
],
"offsets": [
[
525,
535
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7859290_T5"
},
{
"role": "Theme",
"ref_id": "7859290_T7"
}
]
},
{
"id": "7859290_E3",
"type": "Binding",
"trigger": {
"text": [
"associates"
],
"offsets": [
[
525,
535
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7859290_T5"
},
{
"role": "Theme",
"ref_id": "7859290_T6"
}
]
},
{
"id": "7859290_E4",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
622,
629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7859290_T8"
}
]
},
{
"id": "7859290_E5",
"type": "Binding",
"trigger": {
"text": [
"recognizes"
],
"offsets": [
[
643,
653
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7859290_T8"
},
{
"role": "Theme",
"ref_id": "7859290_T9"
},
{
"role": "Site",
"ref_id": "7859290_T20"
}
]
},
{
"id": "7859290_E6",
"type": "Binding",
"trigger": {
"text": [
"recognizes"
],
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643,
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]
]
},
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{
"role": "Theme",
"ref_id": "7859290_T8"
},
{
"role": "Theme",
"ref_id": "7859290_T10"
},
{
"role": "Site",
"ref_id": "7859290_T20"
}
]
},
{
"id": "7859290_E7",
"type": "Binding",
"trigger": {
"text": [
"recognizes"
],
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643,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7859290_T8"
},
{
"role": "Theme",
"ref_id": "7859290_T12"
},
{
"role": "Site",
"ref_id": "7859290_T20"
}
]
},
{
"id": "7859290_E8",
"type": "Binding",
"trigger": {
"text": [
"recognizes"
],
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643,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "7859290_T8"
},
{
"role": "Theme",
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},
{
"role": "Site",
"ref_id": "7859290_T20"
}
]
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{
"id": "7859290_E9",
"type": "Transcription",
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"text": [
"expressed"
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]
]
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"arguments": [
{
"role": "Theme",
"ref_id": "7859290_T13"
}
]
},
{
"id": "7859290_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7859290_T14"
}
]
}
] | [
{
"id": "7859290_1",
"entity_ids": [
"7859290_T4",
"7859290_T5"
]
}
] | [] |
2072454 | 2072454 | [
{
"id": "2072454__text",
"type": "abstract",
"text": [
"Contribution of NF-kappa B and Sp1 binding motifs to the replicative capacity of human immunodeficiency virus type 1: distinct patterns of viral growth are determined by T-cell types. \nStarting with a replication-incompetent molecular clone of human immunodeficiency virus type 1, lacking all the NF-kappa B and Sp1 binding sites present in the native long terminal repeat (LTR), proviruses containing reconstructed LTRs with individual or combinations of NF-kappa B and Sp1 elements were generated and evaluated for their capacity to produce virus progeny following transfection-cocultivation. Virus stocks obtained from these experiments exhibited a continuum of replicative capacities in different human T-cell types depending on which element(s) was present in the LTR. For example, in experiments involving proviral clones with LTRs containing one or two NF-kappa B elements (and no Sp1 binding sites), a hierarchy of cellular permissivity to virus replication (peripheral blood lymphocytes = MT4 greater than H9 greater than CEM greater than Jurkat) was observed. Of note was the associated emergence of second-site LTR revertants which involved an alteration of the TATA box. These results suggest that the human immunodeficiency virus type 1 LTR possesses functional redundancy which ensures virus replication in different T-cell types and is capable of changing depending on the particular combination of transcriptional factors present. "
],
"offsets": [
[
0,
1447
]
]
}
] | [
{
"id": "2072454_T1",
"type": "Protein",
"text": [
"Sp1"
],
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[
31,
34
]
],
"normalized": []
},
{
"id": "2072454_T2",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
312,
315
]
],
"normalized": []
},
{
"id": "2072454_T3",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
471,
474
]
],
"normalized": []
},
{
"id": "2072454_T4",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
888,
891
]
],
"normalized": []
}
] | [] | [] | [] |
10201929 | 10201929 | [
{
"id": "10201929__text",
"type": "abstract",
"text": [
"Engagement of natural cytotoxicity programs regulates AP-1 expression in the NKL human NK cell line. \nNK cell cytotoxicity is a fast and efficient mechanism of target cell lysis. Using transcription analysis, such as multiplex messenger assays, we show here that natural cytotoxicity exerted by the human NKL cell line correlates with mRNA accumulation of very early activator protein (AP)-1 transcription factor genes such as JunB, FosB and c-Fos. In addition, DNA-binding activities of Jun-Fos heterodimers were observed by electrophoretic mobility shift assays during the course of natural cytotoxicity. Interaction between immunoglobulin-like transcript-2/leukocyte Ig-like receptor 1 on NKL cells and HLA-B27 on target cells leads to an impairment of NKL natural cytotoxicity, which correlates with an absence of JunB, FosB, and c-Fos transcription, as well as an absence of their DNA-binding activity. Our studies thus indicate that, despite the rapidity of NK cell-mediated lysis, AP-1 transcription factor is activated during the early stage of NK cell cytolytic programs and that engagement of NK cell inhibitory receptors for MHC class I molecules impairs the very early activation of AP-1. "
],
"offsets": [
[
0,
1201
]
]
}
] | [
{
"id": "10201929_T1",
"type": "Protein",
"text": [
"JunB"
],
"offsets": [
[
427,
431
]
],
"normalized": []
},
{
"id": "10201929_T2",
"type": "Protein",
"text": [
"FosB"
],
"offsets": [
[
433,
437
]
],
"normalized": []
},
{
"id": "10201929_T3",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
442,
447
]
],
"normalized": []
},
{
"id": "10201929_T4",
"type": "Protein",
"text": [
"immunoglobulin-like transcript-2"
],
"offsets": [
[
627,
659
]
],
"normalized": []
},
{
"id": "10201929_T5",
"type": "Protein",
"text": [
"leukocyte Ig-like receptor 1"
],
"offsets": [
[
660,
688
]
],
"normalized": []
},
{
"id": "10201929_T6",
"type": "Protein",
"text": [
"HLA-B27"
],
"offsets": [
[
706,
713
]
],
"normalized": []
},
{
"id": "10201929_T7",
"type": "Protein",
"text": [
"JunB"
],
"offsets": [
[
818,
822
]
],
"normalized": []
},
{
"id": "10201929_T8",
"type": "Protein",
"text": [
"FosB"
],
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824,
828
]
],
"normalized": []
},
{
"id": "10201929_T9",
"type": "Protein",
"text": [
"c-Fos"
],
"offsets": [
[
834,
839
]
],
"normalized": []
}
] | [
{
"id": "10201929_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"mRNA accumulation"
],
"offsets": [
[
335,
352
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10201929_T3"
}
]
},
{
"id": "10201929_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"mRNA accumulation"
],
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335,
352
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10201929_T1"
}
]
},
{
"id": "10201929_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"mRNA accumulation"
],
"offsets": [
[
335,
352
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10201929_T2"
}
]
},
{
"id": "10201929_E4",
"type": "Binding",
"trigger": {
"text": [
"Interaction"
],
"offsets": [
[
607,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10201929_T4"
},
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"role": "Theme",
"ref_id": "10201929_T6"
}
]
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{
"id": "10201929_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"absence"
],
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10201929_E8"
}
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"id": "10201929_E6",
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"text": [
"absence"
],
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]
]
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"role": "Theme",
"ref_id": "10201929_E10"
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],
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]
]
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"role": "Theme",
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"role": "Theme",
"ref_id": "10201929_T8"
}
]
},
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"id": "10201929_E11",
"type": "Negative_regulation",
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"text": [
"absence"
],
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10201929_E15"
}
]
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"id": "10201929_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"absence"
],
"offsets": [
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869,
876
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10201929_E14"
}
]
},
{
"id": "10201929_E13",
"type": "Negative_regulation",
"trigger": {
"text": [
"absence"
],
"offsets": [
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869,
876
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10201929_E16"
}
]
},
{
"id": "10201929_E14",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10201929_T8"
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{
"id": "10201929_E15",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
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890,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "10201929_T7"
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]
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"id": "10201929_E16",
"type": "Binding",
"trigger": {
"text": [
"binding activity"
],
"offsets": [
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890,
906
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10201929_T9"
}
]
}
] | [
{
"id": "10201929_1",
"entity_ids": [
"10201929_T4",
"10201929_T5"
]
}
] | [] |
8473495 | 8473495 | [
{
"id": "8473495__text",
"type": "abstract",
"text": [
"Negative transcriptional regulation of human interleukin 2 (IL-2) gene by glucocorticoids through interference with nuclear transcription factors AP-1 and NF-AT. \nIL-2 gene transcription is affected by several nuclear proteins. We asked whether dexamethasone (Dex) and cyclosporin A (CsA) inhibit IL-2 gene transcription by interfering with the activity of nuclear proteins that bind to the IL-2 promoter. Nuclear extracts from primary human T lymphocytes were analyzed by electrophoretic DNA mobility shift assays. Both Dex and CsA inhibited the binding of transcription factors AP-1 and NF-AT, but not of NF-kB and OCT-1/OAF, to their corresponding sites on the IL-2 gene promoter. To correlate changes in nuclear factor binding in vitro with transcriptional activity in vivo and define the structural requirements for IL-2 promoter repression, we used transient DNA transfections. Jurkat cells were transfected with plasmids containing either the intact IL-2 promoter or its AP-1, NF-AT, and NF-kB motifs. Dex inhibited the IL-2 promoter and the AP-1, but not the NF-AT and NF-kB plasmids. In contrast, CsA inhibited the IL-2 promoter and the NF-AT, but not the AP-1 and NF-kB plasmids. These results suggest that in human T lymphocytes both Dex and CsA inhibited IL-2 gene transcription through interference with transcription factors AP-1 and NF-AT. We propose that, while maximum inhibition may involve interaction with both transcription factors, AP-1 is the primary target of Dex. "
],
"offsets": [
[
0,
1489
]
]
}
] | [
{
"id": "8473495_T1",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
45,
58
]
],
"normalized": []
},
{
"id": "8473495_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
60,
64
]
],
"normalized": []
},
{
"id": "8473495_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
163,
167
]
],
"normalized": []
},
{
"id": "8473495_T4",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
297,
301
]
],
"normalized": []
},
{
"id": "8473495_T5",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
391,
395
]
],
"normalized": []
},
{
"id": "8473495_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
664,
668
]
],
"normalized": []
},
{
"id": "8473495_T7",
"type": "Protein",
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"IL-2"
],
"offsets": [
[
821,
825
]
],
"normalized": []
},
{
"id": "8473495_T8",
"type": "Protein",
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"IL-2"
],
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[
957,
961
]
],
"normalized": []
},
{
"id": "8473495_T9",
"type": "Protein",
"text": [
"IL-2"
],
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[
1027,
1031
]
],
"normalized": []
},
{
"id": "8473495_T10",
"type": "Protein",
"text": [
"IL-2"
],
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1124,
1128
]
],
"normalized": []
},
{
"id": "8473495_T11",
"type": "Protein",
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"IL-2"
],
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[
1267,
1271
]
],
"normalized": []
},
{
"id": "8473495_T18",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
396,
404
]
],
"normalized": []
},
{
"id": "8473495_T21",
"type": "Entity",
"text": [
"their corresponding sites"
],
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[
631,
656
]
],
"normalized": []
},
{
"id": "8473495_T23",
"type": "Entity",
"text": [
"promoter"
],
"offsets": [
[
826,
834
]
],
"normalized": []
}
] | [
{
"id": "8473495_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"Negative transcriptional regulation"
],
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[
0,
35
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_T2"
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},
{
"id": "8473495_E2",
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"text": [
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173,
186
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8473495_T3"
}
]
},
{
"id": "8473495_E3",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
190,
198
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_E2"
}
]
},
{
"id": "8473495_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibit"
],
"offsets": [
[
289,
296
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_E5"
}
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},
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"id": "8473495_E5",
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307,
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"role": "Theme",
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}
]
},
{
"id": "8473495_E6",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
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[
379,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8473495_T5"
},
{
"role": "Site",
"ref_id": "8473495_T18"
}
]
},
{
"id": "8473495_E7",
"type": "Negative_regulation",
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"text": [
"inhibited"
],
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533,
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]
]
},
"arguments": [
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"role": "Theme",
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}
]
},
{
"id": "8473495_E8",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
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547,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_T6"
},
{
"role": "Site",
"ref_id": "8473495_T21"
}
]
},
{
"id": "8473495_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"requirements"
],
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804,
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_E10"
}
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},
{
"id": "8473495_E10",
"type": "Negative_regulation",
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"text": [
"repression"
],
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_T7"
},
{
"role": "Site",
"ref_id": "8473495_T23"
}
]
},
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"id": "8473495_E11",
"type": "Negative_regulation",
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"text": [
"inhibited"
],
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1013,
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]
},
"arguments": [
{
"role": "Theme",
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}
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},
{
"id": "8473495_E12",
"type": "Negative_regulation",
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"text": [
"inhibited"
],
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1110,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_T10"
}
]
},
{
"id": "8473495_E13",
"type": "Negative_regulation",
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"text": [
"inhibited"
],
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1257,
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_E14"
}
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},
{
"id": "8473495_E14",
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},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_T11"
}
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},
{
"id": "8473495_E15",
"type": "Negative_regulation",
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"text": [
"inhibition"
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},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_E14"
}
]
},
{
"id": "8473495_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"involve"
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[
1401,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8473495_E15"
}
]
}
] | [
{
"id": "8473495_1",
"entity_ids": [
"8473495_T1",
"8473495_T2"
]
}
] | [] |
7849291 | 7849291 | [
{
"id": "7849291__text",
"type": "abstract",
"text": [
"Posttranscriptional regulation of macrophage tissue factor expression by antioxidants. \nTissue factor (TF) expression by cells of monocyte/macrophage lineage represents an important mechanism underlying the initiation of fibrin deposition at sites of extravascular inflammation. Recent evidence suggests a role for oxidant stress in the signalling pathway of various cell types by virtue of its ability to induce DNA binding of various transcription factors, including nuclear factor kappa B and AP-1. The effect of antioxidant treatment on lipopolysaccharide (LPS)-induced TF expression was examined in murine peritoneal macrophages and human monocytes. Both pyrrolidine dithiocarbamate, an oxidant scavenger, and N-acetyl-cysteine, a precursor of the endogenous antioxidant glutathione, inhibited stimulation of macrophage procoagulant activity by LPS. Northern blot analysis showed that neither of these agents reduced LPS-stimulated TF mRNA accumulation, thereby suggesting a posttranscriptional mechanism for the effect. Immunofluorescence studies of human monocytes using polyclonal anti-TF antibody showed that N-acetyl-cysteine treatment prevented the characteristic plasmalemmal localization of TF antigen that occurs in response to LPS. Western blot analysis showed that N-acetyl-cysteine reduced the accumulation of the 47-kD mature glycoprotein in LPS-treated cells, a finding consistent with the results of the immunofluorescence studies. Furthermore, these conditions did not result in an accumulation of the less mature forms of TF. When considered together, these data suggest that antioxidants exert their effects by impairing translation and/or by causing degradation of newly translated protein. The effect of antioxidants on tumor necrosis factor appeared to be species specific, with no effect on LPS-induced tumor necrosis factor in murine cells, but with inhibition in human monocytes. The posttranscriptional effect of antioxidants on TF expression data suggests a novel mechanism whereby these agents might modulate monocyte/macrophage activation. "
],
"offsets": [
[
0,
2073
]
]
}
] | [
{
"id": "7849291_T1",
"type": "Protein",
"text": [
"tissue factor"
],
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[
45,
58
]
],
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},
{
"id": "7849291_T2",
"type": "Protein",
"text": [
"Tissue factor"
],
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[
88,
101
]
],
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},
{
"id": "7849291_T3",
"type": "Protein",
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"TF"
],
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[
103,
105
]
],
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},
{
"id": "7849291_T4",
"type": "Protein",
"text": [
"TF"
],
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[
574,
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]
],
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},
{
"id": "7849291_T5",
"type": "Protein",
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"TF"
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937,
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]
],
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},
{
"id": "7849291_T6",
"type": "Protein",
"text": [
"TF"
],
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1094,
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]
],
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},
{
"id": "7849291_T7",
"type": "Protein",
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"TF"
],
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1204,
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]
],
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},
{
"id": "7849291_T8",
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"TF"
],
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1544,
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]
],
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},
{
"id": "7849291_T9",
"type": "Protein",
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"TF"
],
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1959,
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]
],
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},
{
"id": "7849291_T20",
"type": "Entity",
"text": [
"plasmalemmal"
],
"offsets": [
[
1175,
1187
]
],
"normalized": []
}
] | [
{
"id": "7849291_E1",
"type": "Regulation",
"trigger": {
"text": [
"Posttranscriptional regulation"
],
"offsets": [
[
0,
30
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_E2"
}
]
},
{
"id": "7849291_E2",
"type": "Gene_expression",
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"text": [
"expression"
],
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59,
69
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "7849291_T1"
}
]
},
{
"id": "7849291_E3",
"type": "Gene_expression",
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"text": [
"expression"
],
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107,
117
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_T3"
}
]
},
{
"id": "7849291_E4",
"type": "Regulation",
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"text": [
"effect"
],
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506,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "7849291_E5"
}
]
},
{
"id": "7849291_E5",
"type": "Positive_regulation",
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"text": [
"induced"
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "7849291_E6"
}
]
},
{
"id": "7849291_E6",
"type": "Gene_expression",
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"expression"
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "7849291_T4"
}
]
},
{
"id": "7849291_E7",
"type": "Negative_regulation",
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"text": [
"reduced"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_E8"
}
]
},
{
"id": "7849291_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulated"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_E9"
}
]
},
{
"id": "7849291_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"accumulation"
],
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945,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_T5"
}
]
},
{
"id": "7849291_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"prevented"
],
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1146,
1155
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_E12"
}
]
},
{
"id": "7849291_E11",
"type": "Localization",
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"text": [
"localization"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_T7"
},
{
"role": "ToLoc",
"ref_id": "7849291_T20"
}
]
},
{
"id": "7849291_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"occurs"
],
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[
1220,
1226
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_E11"
}
]
},
{
"id": "7849291_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"result"
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_E14"
}
]
},
{
"id": "7849291_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"accumulation"
],
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[
1503,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_T8"
}
]
},
{
"id": "7849291_E15",
"type": "Regulation",
"trigger": {
"text": [
"posttranscriptional effect"
],
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[
1913,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "7849291_E16"
}
]
},
{
"id": "7849291_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7849291_T9"
}
]
}
] | [
{
"id": "7849291_1",
"entity_ids": [
"7849291_T2",
"7849291_T3"
]
}
] | [] |
10079106 | 10079106 | [
{
"id": "10079106__text",
"type": "abstract",
"text": [
"Selective activation and functional significance of p38alpha mitogen-activated protein kinase in lipopolysaccharide-stimulated neutrophils. \nActivation of leukocytes by proinflammatory stimuli selectively initiates intracellular signal transduction via sequential phosphorylation of kinases. Lipopolysaccharide (LPS) stimulation of human neutrophils is known to result in activation of p38 mitogen-activated protein kinase (MAPk); however, the upstream activator(s) of p38 MAPk is unknown, and consequences of p38 MAPk activation remain largely undefined. We investigated the MAPk kinase (MKK) that activates p38 MAPk in response to LPS, the p38 MAPk isoforms that are activated as part of this pathway, and the functional responses affected by p38 MAPk activation. Although MKK3, MKK4, and MKK6 all activated p38 MAPk in experimental models, only MKK3 was found to activate recombinant p38 MAPk in LPS-treated neutrophils. Of p38 MAPk isoforms studied, only p38alpha and p38delta were detected in neutrophils. LPS stimulation selectively activated p38alpha. Specific inhibitors of p38alpha MAPk blocked LPS-induced adhesion, nuclear factor-kappa B (NF-kappaB) activation, and synthesis of tumor necrosis factor-alpha (TNF-alpha). Inhibition of p38alpha MAPk resulted in a transient decrease in TNF-alpha mRNA accumulation but persistent loss of TNF-alpha synthesis. These findings support a pathway by which LPS stimulation of neutrophils results in activation of MKK3, which in turn activates p38alpha MAPk, ultimately regulating adhesion, NF-kappaB activation, enhanced gene expression of TNF-alpha, and regulation of TNF-alpha synthesis. "
],
"offsets": [
[
0,
1642
]
]
}
] | [
{
"id": "10079106_T1",
"type": "Protein",
"text": [
"MKK3"
],
"offsets": [
[
775,
779
]
],
"normalized": []
},
{
"id": "10079106_T2",
"type": "Protein",
"text": [
"MKK4"
],
"offsets": [
[
781,
785
]
],
"normalized": []
},
{
"id": "10079106_T3",
"type": "Protein",
"text": [
"MKK6"
],
"offsets": [
[
791,
795
]
],
"normalized": []
},
{
"id": "10079106_T4",
"type": "Protein",
"text": [
"MKK3"
],
"offsets": [
[
848,
852
]
],
"normalized": []
},
{
"id": "10079106_T5",
"type": "Protein",
"text": [
"p38alpha"
],
"offsets": [
[
959,
967
]
],
"normalized": []
},
{
"id": "10079106_T6",
"type": "Protein",
"text": [
"p38delta"
],
"offsets": [
[
972,
980
]
],
"normalized": []
},
{
"id": "10079106_T7",
"type": "Protein",
"text": [
"p38alpha"
],
"offsets": [
[
1049,
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]
],
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},
{
"id": "10079106_T8",
"type": "Protein",
"text": [
"p38alpha MAPk"
],
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[
1082,
1095
]
],
"normalized": []
},
{
"id": "10079106_T9",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
1190,
1217
]
],
"normalized": []
},
{
"id": "10079106_T10",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1219,
1228
]
],
"normalized": []
},
{
"id": "10079106_T11",
"type": "Protein",
"text": [
"p38alpha MAPk"
],
"offsets": [
[
1245,
1258
]
],
"normalized": []
},
{
"id": "10079106_T12",
"type": "Protein",
"text": [
"TNF-alpha"
],
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[
1295,
1304
]
],
"normalized": []
},
{
"id": "10079106_T13",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1346,
1355
]
],
"normalized": []
},
{
"id": "10079106_T14",
"type": "Protein",
"text": [
"MKK3"
],
"offsets": [
[
1465,
1469
]
],
"normalized": []
},
{
"id": "10079106_T15",
"type": "Protein",
"text": [
"p38alpha MAPk"
],
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[
1495,
1508
]
],
"normalized": []
},
{
"id": "10079106_T16",
"type": "Protein",
"text": [
"TNF-alpha"
],
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[
1592,
1601
]
],
"normalized": []
},
{
"id": "10079106_T17",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1621,
1630
]
],
"normalized": []
}
] | [
{
"id": "10079106_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"detected"
],
"offsets": [
[
986,
994
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T6"
}
]
},
{
"id": "10079106_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"detected"
],
"offsets": [
[
986,
994
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T5"
}
]
},
{
"id": "10079106_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1039,
1048
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T7"
}
]
},
{
"id": "10079106_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitors"
],
"offsets": [
[
1068,
1078
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T8"
}
]
},
{
"id": "10079106_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocked"
],
"offsets": [
[
1096,
1103
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_E6"
},
{
"role": "Cause",
"ref_id": "10079106_E4"
}
]
},
{
"id": "10079106_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"synthesis"
],
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[
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T10"
}
]
},
{
"id": "10079106_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"Inhibition"
],
"offsets": [
[
1231,
1241
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T11"
}
]
},
{
"id": "10079106_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"loss"
],
"offsets": [
[
1338,
1342
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_E9"
},
{
"role": "Cause",
"ref_id": "10079106_E7"
}
]
},
{
"id": "10079106_E9",
"type": "Gene_expression",
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"text": [
"synthesis"
],
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[
1356,
1365
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T13"
}
]
},
{
"id": "10079106_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"results"
],
"offsets": [
[
1440,
1447
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_E11"
}
]
},
{
"id": "10079106_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1451,
1461
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T14"
}
]
},
{
"id": "10079106_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
1485,
1494
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T15"
},
{
"role": "Cause",
"ref_id": "10079106_E10"
}
]
},
{
"id": "10079106_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"enhanced"
],
"offsets": [
[
1564,
1572
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_E14"
},
{
"role": "Cause",
"ref_id": "10079106_E12"
}
]
},
{
"id": "10079106_E14",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1578,
1588
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T16"
}
]
},
{
"id": "10079106_E15",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
1607,
1617
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_E16"
},
{
"role": "Cause",
"ref_id": "10079106_E12"
}
]
},
{
"id": "10079106_E16",
"type": "Gene_expression",
"trigger": {
"text": [
"synthesis"
],
"offsets": [
[
1631,
1640
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10079106_T17"
}
]
}
] | [
{
"id": "10079106_1",
"entity_ids": [
"10079106_T9",
"10079106_T10"
]
}
] | [] |
8627791 | 8627791 | [
{
"id": "8627791__text",
"type": "abstract",
"text": [
"Efficient transcription and replication of simian immunodeficiency virus in the absence of NF-kappaB and Sp1 binding elements. \nTen mutants of the simian immunodeficiency virus (SIV) SIVmac239 bearing deletions (delta) or substitutions (subst) in the NF-kappaB and/or Sp1 binding elements were created, and the replicative capacities of the mutants were analyzed. All mutants, including one extensively mutagenized strain entirely missing the NF-kappaB and four Spl binding elements, replicated with wild-type kinetics and to a wild-type level in peripheral blood mononuclear cell cultures in 50 to 100% of the experiments. One group of mutants replicated very similarly to SIVmac239 in kinetics and yield in CEMxl74 cells (2xNFKappaB > or = SlVmac239 approximately deltaNFkappaB approximately deltaSpl234 approximately substNFkappaB approximately substSpl2 approximately substSp23), while a second group replicated with delayed or slightly delayed kinetics in CEMxl74 cells (SIVmac239 > substSp34 > deltaNFkappaBdeltaSpl234 approximately deltaNFkappaBdeltaSp1 > substSpl234). Reversions or additional mutations were not detected in the U3 and R regions of proviral DNA from CEMxl74 cells infected with the SIVmac239 mutants. Similar results were obtained when mutants of SIVmacMER (a macrophage-competent derivative of SIVmac239) were tested in peripheral blood mononuclear cell and CEMx174 cultures. However, the growth of most mutated viruses was suppressed in primary rhesus monkey alveolar macrophages (SIVmacMER approximately 2xNFkappaB approximately substNFkappaB > deltaNFkappaB > deltaNFkappaBdeltaSpl234 approximately deltaNFkappaBdeltaSpl > deltaSpl234 approximately substSpl2 > substSp23 approximately substSp34 approximately substSpl234 > or = SIVmac239). Thus, changes in the Sp1 binding sites had the most dramatic effects on SIVmac replication in primary macrophage cultures. Analysis of long terminal repeat-driven secreted alkaline phosphatase activity in transient assays showed that, unlike human immunodeficiency virus type 1, the SIV long terminal repeat possesses an enhancer region just upstream of the NF-kappaB element which maintains significant levels of basal transcription in the absence of NF-kappaB and Sp1 sites. This region is responsive to transactivation by Tat. In addition, the SIV TATA box was shown to be stronger than that of human immunodeficiency virus type 1. Therefore, the surprisingly high replicative capacity of NF-kappaB and Sp1 binding site mutants of SIVmac is due to unique features or the enhancer/promoter region. "
],
"offsets": [
[
0,
2569
]
]
}
] | [
{
"id": "8627791_T1",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
105,
108
]
],
"normalized": []
},
{
"id": "8627791_T2",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
268,
271
]
],
"normalized": []
},
{
"id": "8627791_T3",
"type": "Protein",
"text": [
"Spl"
],
"offsets": [
[
462,
465
]
],
"normalized": []
},
{
"id": "8627791_T4",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
1790,
1793
]
],
"normalized": []
},
{
"id": "8627791_T5",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
2235,
2238
]
],
"normalized": []
},
{
"id": "8627791_T6",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
2294,
2297
]
],
"normalized": []
},
{
"id": "8627791_T7",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
2475,
2478
]
],
"normalized": []
}
] | [] | [] | [] |
10377411 | 10377411 | [
{
"id": "10377411__text",
"type": "abstract",
"text": [
"The intracellular parasite Theileria parva protects infected T cells from apoptosis. \nParasites have evolved a plethora of strategies to ensure their survival. The intracellular parasite Theileria parva secures its propagation and spreads through the infected animal by infecting and transforming T cells, inducing their continuous proliferation and rendering them metastatic. In previous work, we have shown that the parasite induces constitutive activation of the transcription factor NF-kappaB, by inducing the constitutive degradation of its cytoplasmic inhibitors. The biological significance of NF-kappaB activation in T. parva-infected cells, however, has not yet been defined. Cells that have been transformed by viruses or oncogenes can persist only if they manage to avoid destruction by the apoptotic mechanisms that are activated on transformation and that contribute to maintain cellular homeostasis. We now demonstrate that parasite-induced NF-kappaB activation plays a crucial role in the survival of T. parva-transformed T cells by conveying protection against an apoptotic signal that accompanies parasite-mediated transformation. Consequently, inhibition of NF-kappaB nuclear translocation and the expression of dominant negative mutant forms of components of the NF-kappaB activation pathway, such as IkappaBalpha or p65, prompt rapid apoptosis of T. parva-transformed T cells. Our findings offer important insights into parasite survival strategies and demonstrate that parasite-induced constitutive NF-kappaB activation is an essential step in maintaining the transformed phenotype of the infected cells. "
],
"offsets": [
[
0,
1626
]
]
}
] | [
{
"id": "10377411_T1",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
1320,
1332
]
],
"normalized": []
},
{
"id": "10377411_T2",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1336,
1339
]
],
"normalized": []
}
] | [] | [] | [] |
7518838 | 7518838 | [
{
"id": "7518838__text",
"type": "abstract",
"text": [
"Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells. \nAntioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood. We have examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in atherosclerotic plaque development, monocyte adhesion to stimulated endothelial cells (ECs). Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion: IL-1 (10 ng/ml), LPS (10 ng/ml), thrombin (30 U/ml), or PMA (10 nM). Agonist-induced monocytic cell adhesion, but not basal adhesion, was inhibited in a time- and concentration-dependent manner by alpha-tcp. The IC50 of alpha-tcp on an IL-1-induced response was 45 microM. The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system. Probucol (50 microM) and N-acetylcysteine (20 mM) also inhibited agonist-induced monocytic cell adhesion; whereas, several other antioxidants had no significant effect. Protein kinase C (PKC) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed. Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC. Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation. It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL--a putative triggering molecule in the atherosclerotic process. Our results point to a novel alternative mechanism of action of alpha-tcp. "
],
"offsets": [
[
0,
1939
]
]
}
] | [
{
"id": "7518838_T1",
"type": "Protein",
"text": [
"E-selectin"
],
"offsets": [
[
890,
900
]
],
"normalized": []
},
{
"id": "7518838_T2",
"type": "Protein",
"text": [
"E-selectin"
],
"offsets": [
[
937,
947
]
],
"normalized": []
},
{
"id": "7518838_T3",
"type": "Protein",
"text": [
"E-selectin"
],
"offsets": [
[
1013,
1023
]
],
"normalized": []
},
{
"id": "7518838_T4",
"type": "Protein",
"text": [
"E-selectin"
],
"offsets": [
[
1495,
1505
]
],
"normalized": []
}
] | [
{
"id": "7518838_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"decrease"
],
"offsets": [
[
855,
863
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518838_T1"
}
]
},
{
"id": "7518838_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"decrease"
],
"offsets": [
[
855,
863
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518838_E3"
}
]
},
{
"id": "7518838_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
923,
933
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518838_T2"
}
]
},
{
"id": "7518838_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"necessary"
],
"offsets": [
[
1462,
1471
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518838_E5"
}
]
},
{
"id": "7518838_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
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1506,
1516
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518838_T4"
}
]
}
] | [] | [] |
9032271 | 9032271 | [
{
"id": "9032271__text",
"type": "abstract",
"text": [
"Characterization of a mutant cell line that does not activate NF-kappaB in response to multiple stimuli. \nNumerous genes required during the immune or inflammation response as well as the adhesion process are regulated by nuclear factor kappaB (NF-kappaB). Associated with its inhibitor, I kappaB, NF-kappaB resides as an inactive form in the cytoplasm. Upon stimulation by various agents, I kappaB is proteolyzed and NF-kappaB translocates to the nucleus, where it activates its target genes. The transduction pathways that lead to I kappaB inactivation remain poorly understood. In this study, we have characterized a cellular mutant, the 70/Z3-derived 1.3E2 murine pre-B cell line, that does not activate NF-kappaB in response to several stimuli. We demonstrate that upon stimulation by lipopolysaccharide, Taxol, phorbol myristate acetate, interleukin-1, or double-stranded RNA, I kappaB alpha is not degraded, as a result of an absence of induced phosphorylation on serines 32 and 36. Neither a mutation in I kappaB alpha nor a mutation in p50 or relA, the two major subunits of NF-kappaB in this cell line, accounts for this phosphorylation defect. As well as culminating in the inducible phosphorylation of I kappaB alpha on serines 32 and 36, all the stimuli that are inactive on 1.3E2 cells exhibit a sensitivity to the antioxidant pyrrolidine dithiocarbamate (PDTC). In contrast, stimuli such as hyperosmotic shock or phosphatase inhibitors, which use PDTC-insensitive pathways, induce I kappaB alpha degradation in 1.3E2. Analysis of the redox status of 1.3E2 does not reveal any difference from wild-type 70Z/3. We also report that the human T-cell leukemia virus type 1 (HTLV-1)-derived Tax trans-activator induces NF-kappaB activity in 1.3E2, suggesting that this viral protein does not operate via the defective pathway. Finally, we show that two other I kappaB molecules, I kappaB beta and the recently identified I kappaB epsilon, are not degraded in the 1.3E2 cell line following stimulation. Our results demonstrate that 1.3E2 is a cellular transduction mutant exhibiting a defect in a step that is required by several different stimuli to activate NF-kappaB. In addition, this analysis suggests a common step in the signaling pathways that trigger I kappaB alpha, I kappaB beta, and I kappaB epsilon degradation. "
],
"offsets": [
[
0,
2333
]
]
}
] | [
{
"id": "9032271_T1",
"type": "Protein",
"text": [
"I kappaB alpha"
],
"offsets": [
[
883,
897
]
],
"normalized": []
},
{
"id": "9032271_T2",
"type": "Protein",
"text": [
"I kappaB alpha"
],
"offsets": [
[
1012,
1026
]
],
"normalized": []
},
{
"id": "9032271_T3",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1045,
1048
]
],
"normalized": []
},
{
"id": "9032271_T4",
"type": "Protein",
"text": [
"relA"
],
"offsets": [
[
1052,
1056
]
],
"normalized": []
},
{
"id": "9032271_T5",
"type": "Protein",
"text": [
"I kappaB alpha"
],
"offsets": [
[
1214,
1228
]
],
"normalized": []
},
{
"id": "9032271_T6",
"type": "Protein",
"text": [
"I kappaB alpha"
],
"offsets": [
[
1496,
1510
]
],
"normalized": []
},
{
"id": "9032271_T7",
"type": "Protein",
"text": [
"Tax"
],
"offsets": [
[
1700,
1703
]
],
"normalized": []
},
{
"id": "9032271_T8",
"type": "Protein",
"text": [
"I kappaB beta"
],
"offsets": [
[
1888,
1901
]
],
"normalized": []
},
{
"id": "9032271_T9",
"type": "Protein",
"text": [
"I kappaB epsilon"
],
"offsets": [
[
1930,
1946
]
],
"normalized": []
},
{
"id": "9032271_T10",
"type": "Protein",
"text": [
"I kappaB alpha"
],
"offsets": [
[
2268,
2282
]
],
"normalized": []
},
{
"id": "9032271_T11",
"type": "Protein",
"text": [
"I kappaB beta"
],
"offsets": [
[
2284,
2297
]
],
"normalized": []
},
{
"id": "9032271_T12",
"type": "Protein",
"text": [
"I kappaB epsilon"
],
"offsets": [
[
2303,
2319
]
],
"normalized": []
},
{
"id": "9032271_T17",
"type": "Entity",
"text": [
"serines 32 and 36"
],
"offsets": [
[
971,
988
]
],
"normalized": []
}
] | [
{
"id": "9032271_E1",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degraded"
],
"offsets": [
[
905,
913
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T1"
}
]
},
{
"id": "9032271_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"result"
],
"offsets": [
[
920,
926
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E1"
},
{
"role": "Cause",
"ref_id": "9032271_E3"
}
]
},
{
"id": "9032271_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"absence"
],
"offsets": [
[
933,
940
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E4"
}
]
},
{
"id": "9032271_E4",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
952,
967
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T1"
},
{
"role": "Site",
"ref_id": "9032271_T17"
}
]
},
{
"id": "9032271_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"accounts for"
],
"offsets": [
[
1113,
1125
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E3"
}
]
},
{
"id": "9032271_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"culminating"
],
"offsets": [
[
1166,
1177
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E7"
}
]
},
{
"id": "9032271_E7",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1195,
1210
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T5"
}
]
},
{
"id": "9032271_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
1489,
1495
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E9"
}
]
},
{
"id": "9032271_E9",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
1511,
1522
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T6"
}
]
},
{
"id": "9032271_E10",
"type": "Regulation",
"trigger": {
"text": [
"operate"
],
"offsets": [
[
1801,
1808
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E4"
},
{
"role": "Cause",
"ref_id": "9032271_T7"
}
]
},
{
"id": "9032271_E11",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degraded"
],
"offsets": [
[
1956,
1964
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T8"
}
]
},
{
"id": "9032271_E12",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degraded"
],
"offsets": [
[
1956,
1964
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T9"
}
]
},
{
"id": "9032271_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"following"
],
"offsets": [
[
1988,
1997
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E12"
}
]
},
{
"id": "9032271_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"following"
],
"offsets": [
[
1988,
1997
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E11"
}
]
},
{
"id": "9032271_E15",
"type": "Positive_regulation",
"trigger": {
"text": [
"trigger"
],
"offsets": [
[
2260,
2267
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E19"
}
]
},
{
"id": "9032271_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"trigger"
],
"offsets": [
[
2260,
2267
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E18"
}
]
},
{
"id": "9032271_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"trigger"
],
"offsets": [
[
2260,
2267
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_E20"
}
]
},
{
"id": "9032271_E18",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
2320,
2331
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T12"
}
]
},
{
"id": "9032271_E19",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
2320,
2331
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T10"
}
]
},
{
"id": "9032271_E20",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
2320,
2331
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032271_T11"
}
]
}
] | [] | [] |
1532661 | 1532661 | [
{
"id": "1532661__text",
"type": "abstract",
"text": [
"An 11-base-pair DNA sequence motif apparently unique to the human interleukin 4 gene confers responsiveness to T-cell activation signals. \nWe have identified a DNA segment that confers responsiveness to antigen stimulation signals on the human interleukin (IL) 4 gene in Jurkat cells. The human IL-4 gene, of 10 kilobases, is composed of four exons and three introns. A cis-acting element (P sequence) resides in the 5' upstream region; no additional DNA segments with enhancer activity were identified in the human IL-4 gene. For further mapping purposes, a fusion promoter was constructed with the granulocyte/macrophage colony-stimulating factor basic promoter containing 60 base pairs of sequence upstream from the cap site of the mouse granulocyte/macrophage colony-stimulating factor gene and various lengths of the 5' upstream sequence of the IL-4 gene. The P sequence was located between positions -79 and -69 relative to the transcription start site of the human IL-4 gene, and this location was confirmed by base-substitution mutations. The plasmids carrying multiple copies of the P sequence showed higher responsiveness to the stimulation. The binding protein(s) that recognize the P sequence of the IL-4 gene were identified by DNA-mobility-shift assays. The binding of NF(P) (a DNA binding protein that specifically recognizes the P sequence) to the P sequence was abolished when oligonucleotides carrying base substitutions were used, indicating that the NF(P) interaction is sequence-specific and that binding specificity of the protein paralleled the sequence requirements for IL-4 expression in vivo. The P sequence does not share homology with the 5' upstream sequence of the IL-2 gene, even though surrounding sequences of the IL-4 gene share high homology with the IL-2 gene. We conclude that a different set of proteins recognize IL-2 and IL-4 genes. "
],
"offsets": [
[
0,
1873
]
]
}
] | [
{
"id": "1532661_T1",
"type": "Protein",
"text": [
"interleukin 4"
],
"offsets": [
[
66,
79
]
],
"normalized": []
},
{
"id": "1532661_T2",
"type": "Protein",
"text": [
"interleukin (IL) 4"
],
"offsets": [
[
244,
262
]
],
"normalized": []
},
{
"id": "1532661_T3",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
295,
299
]
],
"normalized": []
},
{
"id": "1532661_T4",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
516,
520
]
],
"normalized": []
},
{
"id": "1532661_T5",
"type": "Protein",
"text": [
"granulocyte/macrophage colony-stimulating factor"
],
"offsets": [
[
600,
648
]
],
"normalized": []
},
{
"id": "1532661_T6",
"type": "Protein",
"text": [
"granulocyte/macrophage colony-stimulating factor"
],
"offsets": [
[
741,
789
]
],
"normalized": []
},
{
"id": "1532661_T7",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
850,
854
]
],
"normalized": []
},
{
"id": "1532661_T8",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
972,
976
]
],
"normalized": []
},
{
"id": "1532661_T9",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1212,
1216
]
],
"normalized": []
},
{
"id": "1532661_T10",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1594,
1598
]
],
"normalized": []
},
{
"id": "1532661_T11",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1695,
1699
]
],
"normalized": []
},
{
"id": "1532661_T12",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1747,
1751
]
],
"normalized": []
},
{
"id": "1532661_T13",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1786,
1790
]
],
"normalized": []
},
{
"id": "1532661_T14",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1852,
1856
]
],
"normalized": []
},
{
"id": "1532661_T15",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1861,
1865
]
],
"normalized": []
},
{
"id": "1532661_T19",
"type": "Entity",
"text": [
"P sequence"
],
"offsets": [
[
1194,
1204
]
],
"normalized": []
}
] | [
{
"id": "1532661_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"confers"
],
"offsets": [
[
177,
184
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1532661_E2"
}
]
},
{
"id": "1532661_E2",
"type": "Regulation",
"trigger": {
"text": [
"responsiveness"
],
"offsets": [
[
185,
199
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1532661_T2"
}
]
},
{
"id": "1532661_E3",
"type": "Binding",
"trigger": {
"text": [
"recognize"
],
"offsets": [
[
1180,
1189
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1532661_T9"
},
{
"role": "Site",
"ref_id": "1532661_T19"
}
]
},
{
"id": "1532661_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"requirements"
],
"offsets": [
[
1577,
1589
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1532661_E5"
}
]
},
{
"id": "1532661_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1599,
1609
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1532661_T10"
}
]
},
{
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}
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}
]
}
] | [] | [] |
9824485 | 9824485 | [
{
"id": "9824485__text",
"type": "abstract",
"text": [
"Differential effects of protein kinase C inhibitors on fibronectin-induced interleukin-beta gene transcription, protein synthesis and secretion in human monocytic cells. \nHuman monocytic cells express interleukin-1beta (IL-1beta) when stimulated with the extracellular matrix glycoprotein, fibronectin (FN). Protein kinase C (PKC) activation is considered important for this process; however, the metabolic steps at which PKC acts upon to mediate the FN-induced IL-1beta response remain unclear. We performed an analysis of the mechanisms by which two PKC inhibitors, Calphostin C and Staurosporine, prevent the FN-induced IL-1beta response. Both inhibitors blocked the secretion of IL-1beta protein into the media of peripheral blood mononuclear cells exposed to FN. Immunoprecipitation analysis revealed that under these circumstances, Calphostin C inhibited the production of IL-1beta protein, whereas Staurosporine allowed protein production, but inhibited its secretion. To determine the mechanisms responsible for these differences, we turned to human U937 promonocytic cells. U937 cells transfected with the human full-length IL-1beta promoter connected to a luciferase reporter gene were submitted to transcription assays, Northern blotting, and DNA electrophoresis mobility gel shift assays. These studies revealed that Calphostin C inhibited the nuclear translocation of the transcription factor activator protein-1 (AP-1) which is considered necessary for FN induction of IL-1beta gene transcription, and prevented the transcription of the IL-1beta gene. In contrast, Staurosporine alone induced AP-1 translocation and stimulation of the gene. Overall, our data indicate that Calphostin C prevents the transcription of the IL-1beta gene thereby inhibiting protein synthesis. Based on the high specificity of this compound for PKC, we conclude that PKC is necessary for FN-induced IL-1beta protein production. In contrast, Staurosporine prevented secretion of IL-1beta by unknown mechanisms. "
],
"offsets": [
[
0,
2002
]
]
}
] | [
{
"id": "9824485_T1",
"type": "Protein",
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"fibronectin"
],
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55,
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]
],
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],
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75,
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]
],
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],
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201,
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"FN"
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"FN"
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],
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]
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"FN"
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"FN"
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"id": "9824485_T20",
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},
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"id": "9824485_T21",
"type": "Protein",
"text": [
"IL-1beta"
],
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[
1970,
1978
]
],
"normalized": []
}
] | [
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"effects"
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}
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"blocked"
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]
]
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"role": "Theme",
"ref_id": "9824485_E16"
}
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"type": "Localization",
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"secretion"
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]
]
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"role": "Theme",
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}
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]
]
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"role": "Theme",
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}
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"type": "Negative_regulation",
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],
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]
]
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"role": "Theme",
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"production"
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]
]
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"role": "Theme",
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}
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]
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"role": "Theme",
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]
]
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]
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"inhibited"
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]
]
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"role": "Theme",
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]
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"role": "Theme",
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]
]
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"role": "Theme",
"ref_id": "9824485_E24"
}
]
},
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"induction"
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]
]
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"role": "Theme",
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},
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]
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"role": "Theme",
"ref_id": "9824485_E29"
}
]
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"text": [
"stimulation"
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]
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"role": "Theme",
"ref_id": "9824485_T17"
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"prevents"
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]
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"role": "Theme",
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]
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"role": "Theme",
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"type": "Gene_expression",
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"synthesis"
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]
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"role": "Theme",
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}
]
},
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]
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"role": "Theme",
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]
},
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"induced"
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]
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"role": "Theme",
"ref_id": "9824485_E36"
},
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},
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"type": "Gene_expression",
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"production"
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]
},
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"role": "Theme",
"ref_id": "9824485_T20"
}
]
},
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"id": "9824485_E37",
"type": "Negative_regulation",
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"text": [
"prevented"
],
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]
]
},
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{
"role": "Theme",
"ref_id": "9824485_E38"
}
]
},
{
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"type": "Localization",
"trigger": {
"text": [
"secretion"
],
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9824485_T21"
}
]
}
] | [
{
"id": "9824485_1",
"entity_ids": [
"9824485_T3",
"9824485_T4"
]
},
{
"id": "9824485_2",
"entity_ids": [
"9824485_T5",
"9824485_T6"
]
}
] | [] |
10229820 | 10229820 | [
{
"id": "10229820__text",
"type": "abstract",
"text": [
"Fibroblast growth factor-1 (FGF-1) enhances IL-2 production and nuclear translocation of NF-kappaB in FGF receptor-bearing Jurkat T cells. \nFibroblast growth factors (FGFs) are heparin-binding proteins crucial to embryogenesis, angiogenesis, and wound healing. FGF-1 is abundantly expressed in the synovium in rheumatoid arthritis and in rejecting allografts, sites of chronic immune-mediated inflammation. The frequency of FGF-1-responsive T cells is increased in the peripheral blood of these disorders, and a high percentage of infiltrating T cells in rheumatoid arthritis synovium express receptors for FGF-1. To understand the action of FGF-1 in T cells, studies were initiated in Jurkat T cells that express the signaling isoform of FGF receptor-1. These experiments show that FGF-1 stimulation of Jurkat T cells provides a second signal that augments TCR-mediated IL-2 production. Analogous to costimulation via CD28, this activity is mediated through activation of Rel/kappaB, a family of transcription factors known to regulate IL-2 and other activation-inducible proteins. FGF-1 alone induces modest nuclear translocation of kappaB-binding proteins, and this translocation is enhanced by the combination of anti-CD3 and FGF-1. This NF-kappaB binding complex is composed of transcriptionally active p65(RelA)/p50 heterodimers and results primarily from the targeted degradation of IkappaB-alpha, an inhibitor that sequesters Rel/kappaB in the cytoplasm. These data are the first to show a connection between FGF-1 signaling and NF-kappaB activation outside of embryonic development. The signaling events that link FGF receptor-1 engagement and NF-kappaB activation in Jurkat are probably distinct from the CD28 costimulation pathway, since FGF-1-induced Rel/kappaB binding proteins do not contain significant levels of c-Rel and are not identical with the CD28 response complex. "
],
"offsets": [
[
0,
1888
]
]
}
] | [
{
"id": "10229820_T1",
"type": "Protein",
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"Fibroblast growth factor-1"
],
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[
0,
26
]
],
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},
{
"id": "10229820_T2",
"type": "Protein",
"text": [
"FGF-1"
],
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28,
33
]
],
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},
{
"id": "10229820_T3",
"type": "Protein",
"text": [
"IL-2"
],
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44,
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]
],
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},
{
"id": "10229820_T4",
"type": "Protein",
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261,
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],
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},
{
"id": "10229820_T5",
"type": "Protein",
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"FGF-1"
],
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424,
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]
],
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},
{
"id": "10229820_T6",
"type": "Protein",
"text": [
"FGF-1"
],
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607,
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]
],
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},
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"id": "10229820_T7",
"type": "Protein",
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"FGF-1"
],
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642,
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]
],
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"id": "10229820_T8",
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"FGF receptor-1"
],
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739,
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],
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},
{
"id": "10229820_T9",
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"FGF-1"
],
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783,
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],
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},
{
"id": "10229820_T10",
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"IL-2"
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1865,
1869
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"degradation"
],
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1386
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]
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"engagement"
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]
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}
] | [
{
"id": "10229820_1",
"entity_ids": [
"10229820_T1",
"10229820_T2"
]
}
] | [] |
8144878 | 8144878 | [
{
"id": "8144878__text",
"type": "abstract",
"text": [
"Expression of v-src in T cells correlates with nuclear expression of NF-kappa B. \nNF-kappa B is a rapidly inducible transcriptional activator that responds to a variety of signals and influences the expression of many genes involved in the immune response. Protein tyrosine kinases transmit signals from cytokine and immune receptors. Very little information exists linking these two important classes of signaling molecules. We now demonstrate that v-src expression correlates with nuclear expression of a kappa B binding complex similar to that induced by phorbol ester and ionomycin, as detected by electrophoretic mobility shift assay using a variety of kappa B sites. This complex was blocked by the tyrosine kinase inhibitor, herbimycin A. The v-src-induced complex comprised the p50 and p65 components of NF-kappa B, as determined by supershift and immunoblot analysis. As a functional correlate of this finding, transient co-transfection of HIV-1 LTR reporter constructs in a different T cell line demonstrated that v-src activated this promoter in a kappa B-dependent manner. We found that transactivation of the HIV-1 LTR by v-src was more sensitive to mutations of the proximal, rather than the distal, kappa B element. The implications for T cell receptor signaling and HIV-1 gene expression are considered. "
],
"offsets": [
[
0,
1320
]
]
}
] | [
{
"id": "8144878_T1",
"type": "Protein",
"text": [
"v-src"
],
"offsets": [
[
14,
19
]
],
"normalized": []
},
{
"id": "8144878_T2",
"type": "Protein",
"text": [
"v-src"
],
"offsets": [
[
450,
455
]
],
"normalized": []
},
{
"id": "8144878_T3",
"type": "Protein",
"text": [
"v-src"
],
"offsets": [
[
750,
755
]
],
"normalized": []
},
{
"id": "8144878_T4",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
786,
789
]
],
"normalized": []
},
{
"id": "8144878_T5",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
794,
797
]
],
"normalized": []
},
{
"id": "8144878_T6",
"type": "Protein",
"text": [
"v-src"
],
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[
1024,
1029
]
],
"normalized": []
},
{
"id": "8144878_T7",
"type": "Protein",
"text": [
"v-src"
],
"offsets": [
[
1135,
1140
]
],
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}
] | [
{
"id": "8144878_E1",
"type": "Gene_expression",
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"Expression"
],
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0,
10
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]
},
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"id": "8144878_E2",
"type": "Gene_expression",
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"expression"
],
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]
]
},
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"role": "Theme",
"ref_id": "8144878_T2"
}
]
},
{
"id": "8144878_E3",
"type": "Binding",
"trigger": {
"text": [
"induced complex"
],
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8144878_T4"
},
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"ref_id": "8144878_T5"
}
]
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"id": "8144878_E4",
"type": "Positive_regulation",
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"text": [
"induced"
],
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8144878_E3"
},
{
"role": "Cause",
"ref_id": "8144878_T3"
}
]
}
] | [] | [] |
7882168 | 7882168 | [
{
"id": "7882168__text",
"type": "abstract",
"text": [
"HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. \nNef of primate lentiviruses is required for viremia and progression to AIDS in monkeys. Negative, positive, and no effects of Nef have also been reported on viral replication in cells. To reconcile these observations, we expressed a hybrid CD8-Nef protein in Jurkat cells. Two opposite phenotypes were found, which depended on the intracellular localization of Nef. Expressed in the cytoplasm or on the cell surface, the chimera inhibited or activated early signaling events from the T cell antigen receptor. Activated Jurkat cells died by apoptosis, and only cells with mutated nef genes expressing truncated Nefs survived, which rendered Nef nonfunctional. These mutations paralleled those in other viral strains passaged in vitro. Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation, but they also explain effects of Nef in HIV infection and progression to AIDS. "
],
"offsets": [
[
0,
1047
]
]
}
] | [
{
"id": "7882168_T1",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
6,
9
]
],
"normalized": []
},
{
"id": "7882168_T2",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
101,
104
]
],
"normalized": []
},
{
"id": "7882168_T3",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
227,
230
]
],
"normalized": []
},
{
"id": "7882168_T4",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
345,
348
]
],
"normalized": []
},
{
"id": "7882168_T5",
"type": "Protein",
"text": [
"Nef"
],
"offsets": [
[
462,
465
]
],
"normalized": []
},
{
"id": "7882168_T6",
"type": "Protein",
"text": [
"nef"
],
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[
680,
683
]
],
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},
{
"id": "7882168_T7",
"type": "Protein",
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"Nef"
],
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711,
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]
],
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},
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"id": "7882168_T8",
"type": "Protein",
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"Nef"
],
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741,
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]
],
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},
{
"id": "7882168_T9",
"type": "Protein",
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"Nef"
],
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875,
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]
],
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},
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"id": "7882168_T10",
"type": "Protein",
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],
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911,
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},
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"id": "7882168_T11",
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],
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1001,
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]
],
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},
{
"id": "7882168_T12",
"type": "Entity",
"text": [
"intracellular"
],
"offsets": [
[
72,
85
]
],
"normalized": []
},
{
"id": "7882168_T14",
"type": "Entity",
"text": [
"intracellular"
],
"offsets": [
[
432,
445
]
],
"normalized": []
}
] | [
{
"id": "7882168_E1",
"type": "Localization",
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"text": [
"localization"
],
"offsets": [
[
86,
98
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "7882168_T1"
},
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"role": "AtLoc",
"ref_id": "7882168_T12"
}
]
},
{
"id": "7882168_E2",
"type": "Localization",
"trigger": {
"text": [
"localization"
],
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446,
458
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]
},
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"role": "Theme",
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},
{
"role": "AtLoc",
"ref_id": "7882168_T14"
}
]
},
{
"id": "7882168_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expressing"
],
"offsets": [
[
690,
700
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7882168_T7"
}
]
}
] | [] | [] |
8443122 | 8443122 | [
{
"id": "8443122__text",
"type": "abstract",
"text": [
"Expression of PILOT, a putative transcription factor, requires two signals and is cyclosporin A sensitive in T cells. \nFew known genes (IL-2, members of the IL-8 family, interferon-gamma) are induced in T cells only through the combined effect of phorbol myristic acetate (PMA) and a Ca(2+)-ionophore, and expression of only these genes can be fully suppressed by Cyclosporin A (CyA). We have identified a putative transcription factor, designated PILOT, with an identical dual signal requirement for expression. Induction of the PILOT gene is detectable in human T cells 20 min following activation in the presence of cycloheximide and is fully suppressed by CyA. The PILOT protein has a calculated M(r) of 42.6 kDa and contains three zinc fingers of the C2H2-type at the carboxyl-terminus which are highly homologous to the zinc finger regions of the transcription factors EGR1, EGR2, and pAT 133. In contrast to T cells, in fibroblasts PILOT gene expression requires only one signal (PMA) and is not affected by CyA. This observation directly demonstrates the existence of a Ca2+ signal-dependent regulatory element obligatory for expression of some genes in T cells but not in fibroblasts. This differential expression model will be valuable in the dissection of the dual signal pathway in T cells and the effects of CyA upon it. "
],
"offsets": [
[
0,
1334
]
]
}
] | [
{
"id": "8443122_T1",
"type": "Protein",
"text": [
"PILOT"
],
"offsets": [
[
14,
19
]
],
"normalized": []
},
{
"id": "8443122_T2",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
136,
140
]
],
"normalized": []
},
{
"id": "8443122_T3",
"type": "Protein",
"text": [
"interferon-gamma"
],
"offsets": [
[
170,
186
]
],
"normalized": []
},
{
"id": "8443122_T4",
"type": "Protein",
"text": [
"PILOT"
],
"offsets": [
[
448,
453
]
],
"normalized": []
},
{
"id": "8443122_T5",
"type": "Protein",
"text": [
"PILOT"
],
"offsets": [
[
530,
535
]
],
"normalized": []
},
{
"id": "8443122_T6",
"type": "Protein",
"text": [
"PILOT"
],
"offsets": [
[
669,
674
]
],
"normalized": []
},
{
"id": "8443122_T7",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
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875,
879
]
],
"normalized": []
},
{
"id": "8443122_T8",
"type": "Protein",
"text": [
"EGR2"
],
"offsets": [
[
881,
885
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],
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},
{
"id": "8443122_T9",
"type": "Protein",
"text": [
"pAT 133"
],
"offsets": [
[
891,
898
]
],
"normalized": []
},
{
"id": "8443122_T10",
"type": "Protein",
"text": [
"PILOT"
],
"offsets": [
[
939,
944
]
],
"normalized": []
}
] | [
{
"id": "8443122_E1",
"type": "Gene_expression",
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"text": [
"Expression"
],
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0,
10
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]
},
"arguments": [
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"role": "Theme",
"ref_id": "8443122_T1"
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{
"id": "8443122_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"requires"
],
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54,
62
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8443122_E1"
}
]
},
{
"id": "8443122_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
192,
199
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8443122_T3"
}
]
},
{
"id": "8443122_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
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192,
199
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8443122_T2"
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]
},
{
"id": "8443122_E5",
"type": "Gene_expression",
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"text": [
"expression"
],
"offsets": [
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306,
316
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]
},
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{
"role": "Theme",
"ref_id": "8443122_T3"
}
]
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"id": "8443122_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
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306,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8443122_T2"
}
]
},
{
"id": "8443122_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"suppressed"
],
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[
350,
360
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8443122_E6"
}
]
},
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"id": "8443122_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"suppressed"
],
"offsets": [
[
350,
360
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8443122_E5"
}
]
},
{
"id": "8443122_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"requirement"
],
"offsets": [
[
485,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8443122_E10"
}
]
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"id": "8443122_E10",
"type": "Gene_expression",
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"text": [
"expression"
],
"offsets": [
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501,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8443122_T4"
}
]
},
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"id": "8443122_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"Induction"
],
"offsets": [
[
513,
522
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8443122_T5"
}
]
},
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"id": "8443122_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"suppressed"
],
"offsets": [
[
646,
656
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8443122_E11"
}
]
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"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
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950,
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]
},
"arguments": [
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"role": "Theme",
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}
]
},
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"type": "Positive_regulation",
"trigger": {
"text": [
"requires"
],
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961,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8443122_E13"
}
]
},
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"id": "8443122_E15",
"type": "Regulation",
"trigger": {
"text": [
"affected"
],
"offsets": [
[
1003,
1011
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8443122_E13"
}
]
}
] | [] | [] |
7662982 | 7662982 | [
{
"id": "7662982__text",
"type": "abstract",
"text": [
"TCL1 oncogene activation in preleukemic T cells from a case of ataxia-telangiectasia. \nThe TCL1 oncogene on human chromosome 14q32.1 is involved in chromosome translocations [t(14;14)(q11;q32.1) and t(7;14)(q35;q32.1)] and inversions [inv14(q11;q32.1)] with TCR alpha/beta loci in T-cell leukemias, such as T-prolymphocytic (T-PLL). It is also involved in T- acute and- chronic leukemias arising in cases of ataxia-telangiectasia (AT), an immunodeficiency syndrome. Similar chromosomal rearrangements occur also in the clonally expanded T cells in AT patients before the appearance of the overt leukemia. We have analyzed the expression of TCL1 mRNA and protein in peripheral blood lymphocytes (PBLs) from four AT cases and from healthy controls. We found that the TCL1 gene was overexpressed in the PBLs of an AT patient with a large clonal T-cell population exhibiting the t(14;14) translocation but not in the lymphocytes of the other cases. Fluorescence in situ hybridization of the TCL1 genomic locus to lymphocyte metaphases from the AT patient with the T-cell clonal expansion showed that the breakpoint of the t(14;14) translocation lies within the TCL1 locus and is accompanied by an inverted duplication of the distal part of chromosome 14. These data indicate that TCL1 is activated in preleukemic clonal cells as a consequence of chromosome translocation involving sequences from the TCR locus at 14q11. Deregulation of TCL1 is the first event in the initiation of malignancy in these types of leukemias and represents a potential tool for clinical evaluation. "
],
"offsets": [
[
0,
1573
]
]
}
] | [
{
"id": "7662982_T1",
"type": "Protein",
"text": [
"TCL1"
],
"offsets": [
[
0,
4
]
],
"normalized": []
},
{
"id": "7662982_T2",
"type": "Protein",
"text": [
"TCL1"
],
"offsets": [
[
91,
95
]
],
"normalized": []
},
{
"id": "7662982_T3",
"type": "Protein",
"text": [
"TCL1"
],
"offsets": [
[
640,
644
]
],
"normalized": []
},
{
"id": "7662982_T4",
"type": "Protein",
"text": [
"TCL1"
],
"offsets": [
[
765,
769
]
],
"normalized": []
},
{
"id": "7662982_T5",
"type": "Protein",
"text": [
"TCL1"
],
"offsets": [
[
987,
991
]
],
"normalized": []
},
{
"id": "7662982_T6",
"type": "Protein",
"text": [
"TCL1"
],
"offsets": [
[
1157,
1161
]
],
"normalized": []
},
{
"id": "7662982_T7",
"type": "Protein",
"text": [
"TCL1"
],
"offsets": [
[
1276,
1280
]
],
"normalized": []
},
{
"id": "7662982_T8",
"type": "Protein",
"text": [
"TCL1"
],
"offsets": [
[
1432,
1436
]
],
"normalized": []
}
] | [
{
"id": "7662982_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
14,
24
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7662982_T1"
}
]
},
{
"id": "7662982_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
626,
636
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7662982_T3"
}
]
},
{
"id": "7662982_E3",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
626,
636
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7662982_T3"
}
]
},
{
"id": "7662982_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"overexpressed"
],
"offsets": [
[
779,
792
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7662982_E5"
}
]
},
{
"id": "7662982_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"overexpressed"
],
"offsets": [
[
779,
792
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7662982_T4"
}
]
},
{
"id": "7662982_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1284,
1293
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7662982_T7"
}
]
},
{
"id": "7662982_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"as a consequence of"
],
"offsets": [
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1322,
1341
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7662982_E6"
}
]
},
{
"id": "7662982_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"Deregulation"
],
"offsets": [
[
1416,
1428
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7662982_T8"
}
]
}
] | [] | [] |
7713868 | 7713868 | [
{
"id": "7713868__text",
"type": "abstract",
"text": [
"Platelet-activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes. Correlation with an increased kappa B binding activity. \nHuman peripheral blood monocytes responded to stimulation of platelet-activating factor (PAF) with up-regulation of the transcript for heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent mitogen for vascular smooth muscle cells. This function of PAF was observed at nanomolar concentrations of the ligand, starting at 30 min after stimulation. The PAF-induced up-regulation of HB-EGF mRNA was accompanied by an increase in kappa B binding activity. These functions of PAF appeared to be mediated through the cell surface PAF receptors, as two PAF receptor antagonists, WEB 2086 and L-659,989, blocked both the up-regulation of HB-EGF mRNA and kappa B binding activity induced by PAF. The antagonists, however, had no effect on phorbol ester-induced up-regulation of HB-EGF mRNA and kappa B binding activity. Pretreatment of monocytes with pertussis toxin inhibited these functions of PAF, whereas cholera toxin had no inhibitory effect. Pyrrolidine dithiocarbamate, an inhibitor for NF-kappa B activation, markedly reduced PAF-stimulated kappa B binding activity as well as up-regulation of HB-EGF mRNA. These results suggest a potential role of PAF in HB-EGF expression and provide evidence that this stimulation may occur through increased kappa B binding activity. "
],
"offsets": [
[
0,
1483
]
]
}
] | [
{
"id": "7713868_T1",
"type": "Protein",
"text": [
"heparin-binding epidermal growth factor-like growth factor"
],
"offsets": [
[
59,
117
]
],
"normalized": []
},
{
"id": "7713868_T2",
"type": "Protein",
"text": [
"heparin-binding epidermal growth factor-like growth factor"
],
"offsets": [
[
324,
382
]
],
"normalized": []
},
{
"id": "7713868_T3",
"type": "Protein",
"text": [
"HB-EGF"
],
"offsets": [
[
384,
390
]
],
"normalized": []
},
{
"id": "7713868_T4",
"type": "Protein",
"text": [
"HB-EGF"
],
"offsets": [
[
592,
598
]
],
"normalized": []
},
{
"id": "7713868_T5",
"type": "Protein",
"text": [
"HB-EGF"
],
"offsets": [
[
842,
848
]
],
"normalized": []
},
{
"id": "7713868_T6",
"type": "Protein",
"text": [
"HB-EGF"
],
"offsets": [
[
981,
987
]
],
"normalized": []
},
{
"id": "7713868_T7",
"type": "Protein",
"text": [
"HB-EGF"
],
"offsets": [
[
1306,
1312
]
],
"normalized": []
},
{
"id": "7713868_T8",
"type": "Protein",
"text": [
"HB-EGF"
],
"offsets": [
[
1368,
1374
]
],
"normalized": []
}
] | [
{
"id": "7713868_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"stimulates"
],
"offsets": [
[
27,
37
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E2"
}
]
},
{
"id": "7713868_E2",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
38,
51
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_T1"
}
]
},
{
"id": "7713868_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
288,
301
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_T2"
}
]
},
{
"id": "7713868_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
575,
588
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_T4"
}
]
},
{
"id": "7713868_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
702,
710
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E4"
}
]
},
{
"id": "7713868_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"blocked"
],
"offsets": [
[
808,
815
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E7"
}
]
},
{
"id": "7713868_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
825,
838
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_T5"
}
]
},
{
"id": "7713868_E8",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
932,
938
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E9"
}
]
},
{
"id": "7713868_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
964,
977
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_T6"
}
]
},
{
"id": "7713868_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1070,
1079
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E4"
}
]
},
{
"id": "7713868_E11",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitory effect"
],
"offsets": [
[
1133,
1150
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E4"
}
]
},
{
"id": "7713868_E12",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduced"
],
"offsets": [
[
1230,
1237
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E13"
}
]
},
{
"id": "7713868_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulation"
],
"offsets": [
[
1289,
1302
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_T7"
}
]
},
{
"id": "7713868_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"potential role"
],
"offsets": [
[
1343,
1357
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E15"
}
]
},
{
"id": "7713868_E15",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1375,
1385
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_T8"
}
]
},
{
"id": "7713868_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"occur"
],
"offsets": [
[
1433,
1438
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7713868_E14"
}
]
}
] | [
{
"id": "7713868_1",
"entity_ids": [
"7713868_T2",
"7713868_T3"
]
}
] | [] |
7594456 | 7594456 | [
{
"id": "7594456__text",
"type": "abstract",
"text": [
"Activation of the signal transducer and transcription (STAT) signaling pathway in a primary T cell response. Critical role for IL-6. \nThe T cell activation is initiated by interaction of specific Ags with TCR, followed by activation of intracellular biochemical events leading to activation of several genes. The activation of signal transducer and activator of transcription (STAT) proteins in a primary TCR-mediated activation of T cells have been explored. In purified human peripheral blood T cells, nuclear STAT proteins were activated approximately 3 h after activation by cross-linked anti-CD3 Abs. These STAT proteins were detected by using the IFN-gamma-activated sequence (GAS) and related oligonucleotides as probes in electrophoretic mobility shift assay. Analysis of the nuclear extracts with anti-STAT Abs indicated that they contained STAT-3 and additional proteins crossreactive with the STAT family. The induction of STAT activity was inhibited completely by pretreatment with either cycloheximide or cyclosporin A, thus indicating that the induction was due to a secondary factor produced by the activated T cells. As neutralizing anti-IL-6 Abs effectively down-regulated the early induction of STAT proteins and as exogenously added IL-6 rapidly activated DNA binding similar to TCR-mediated bindings, it can be concluded that IL-6 is the factor responsible for the activation of STAT proteins in a primary T cell response. "
],
"offsets": [
[
0,
1443
]
]
}
] | [
{
"id": "7594456_T1",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
127,
131
]
],
"normalized": []
},
{
"id": "7594456_T2",
"type": "Protein",
"text": [
"Ags"
],
"offsets": [
[
196,
199
]
],
"normalized": []
},
{
"id": "7594456_T3",
"type": "Protein",
"text": [
"CD3"
],
"offsets": [
[
597,
600
]
],
"normalized": []
},
{
"id": "7594456_T4",
"type": "Protein",
"text": [
"STAT-3"
],
"offsets": [
[
850,
856
]
],
"normalized": []
},
{
"id": "7594456_T5",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1154,
1158
]
],
"normalized": []
},
{
"id": "7594456_T6",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1252,
1256
]
],
"normalized": []
},
{
"id": "7594456_T7",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1346,
1350
]
],
"normalized": []
}
] | [
{
"id": "7594456_E1",
"type": "Binding",
"trigger": {
"text": [
"interaction"
],
"offsets": [
[
172,
183
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594456_T2"
}
]
},
{
"id": "7594456_E2",
"type": "Regulation",
"trigger": {
"text": [
"followed"
],
"offsets": [
[
210,
218
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594456_E1"
}
]
},
{
"id": "7594456_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1265,
1274
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7594456_T6"
}
]
}
] | [] | [] |
8664547 | 8664547 | [
{
"id": "8664547__text",
"type": "abstract",
"text": [
"The role of BSAP (Pax-5) in B-cell development. \nThe hierarchy of transcriptional control in B-cell development has recently been analyzed by targeted gene inactivation in the mouse. In this manner, the paired box containing gene Pax-5, encoding the B cell specific transcription factor BSAP, has been shown to play a key role in early B lymphopoiesis. Other experimental strategies have implicated BSAP in the control of cell proliferation, isotype switching and transcription of the immunoglobulin heavy-chain gene at late stages of B-cell differentiation. "
],
"offsets": [
[
0,
559
]
]
}
] | [
{
"id": "8664547_T1",
"type": "Protein",
"text": [
"BSAP"
],
"offsets": [
[
12,
16
]
],
"normalized": []
},
{
"id": "8664547_T2",
"type": "Protein",
"text": [
"Pax-5"
],
"offsets": [
[
18,
23
]
],
"normalized": []
},
{
"id": "8664547_T3",
"type": "Protein",
"text": [
"Pax-5"
],
"offsets": [
[
230,
235
]
],
"normalized": []
},
{
"id": "8664547_T4",
"type": "Protein",
"text": [
"B cell specific transcription factor"
],
"offsets": [
[
250,
286
]
],
"normalized": []
},
{
"id": "8664547_T5",
"type": "Protein",
"text": [
"BSAP"
],
"offsets": [
[
287,
291
]
],
"normalized": []
},
{
"id": "8664547_T6",
"type": "Protein",
"text": [
"BSAP"
],
"offsets": [
[
399,
403
]
],
"normalized": []
}
] | [] | [
{
"id": "8664547_1",
"entity_ids": [
"8664547_T1",
"8664547_T2"
]
},
{
"id": "8664547_2",
"entity_ids": [
"8664547_T4",
"8664547_T5"
]
}
] | [] |
9916078 | 9916078 | [
{
"id": "9916078__text",
"type": "abstract",
"text": [
"Involvement of mitogen-activated protein kinase pathways in interleukin-8 production by human monocytes and polymorphonuclear cells stimulated with lipopolysaccharide or Mycoplasma fermentans membrane lipoproteins. \nInterleukin-8 (IL-8) is a chemokine that belongs to the alpha-chemokine or CXC subfamily and is produced by a wide variety of human cells, including monocytes and polymorphonuclear cells (PMN). IL-8 is secreted in response to inflammatory stimuli, notably bacterial products such as lipopolysaccharide (LPS), but little is known about the mechanisms by which these agents mediate IL-8 induction. In this report, we show that Mycoplasma fermentans lipid-associated membrane proteins (LAMPf) induce the production of high levels of IL-8 by THP-1 (human monocyte) cells and PMN at the same extent as LPS. It was previously demonstrated that stimulation of monocytic cells with either LPS or LAMPf led to a series of common downstream signaling events, including the activation of protein tyrosine kinase and of mitogen-activated protein kinase cascades. By using PD-98059 and SB203580, two potent and selective inhibitors of MEK1 (a kinase upstream of ERK1/2) and p38, respectively, we have demonstrated that both ERK1/2 and p38 cascades play a key role in the production of IL-8 by monocytes and PMN stimulated with bacterial fractions. "
],
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[
0,
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0,
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] | [
{
"id": "9916078_1",
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"9916078_T3"
]
}
] | [] |
8816467 | 8816467 | [
{
"id": "8816467__text",
"type": "abstract",
"text": [
"Induction of bcl-2 expression by phosphorylated CREB proteins during B-cell activation and rescue from apoptosis. \nEngagement of surface immunoglobulin on mature B cells leads to rescue from apoptosis and to proliferation. Levels of bcl-2 mRNA and protein increase with cross-linking of surface immunoglobulin. We have located the major positive regulatory region for control of bcl-2 expression in B cells in the 5'-flanking region. The positive region can be divided into an upstream and a downstream regulatory region. The downstream regulatory region contains a cyclic AMP-responsive element (CRE). We show by antibody supershift experiments and UV cross-linking followed by denaturing polyacrylamide gel electrophoresis that both CREB and ATF family members bind to this region in vitro. Mutations of the CRE site that result in loss of CREB binding also lead to loss of functional activity of the bcl-2 promoter in transient-transfection assays. The presence of an active CRE site in the bcl-2 promoter implies that the regulation of bcl-2 expression is linked to a signal transduction pathway in B cells. Treatment of the mature B-cell line BAL-17 with either anti-immunoglobulin M or phorbol 12-myristate 13-acetate leads to an increase in bcl-2 expression that is mediated by the CRE site. Treatment of the more immature B-cell line, Ramos, with phorbol esters rescues the cells from calcium-dependent apoptosis. bcl-2 expression is increased following phorbol ester treatment, and the increased expression is dependent on the CRE site. These stimuli result in phosphorylation of CREB at serine 133. The phosphorylation of CREB that results in activation is mediated by protein kinase C rather than by protein kinase A. Although the CRE site is necessary, optimal induction of bcl-2 expression requires participation of the upstream regulatory element, suggesting that phosphorylation of CREB alters its interaction with the upstream regulatory element. The CRE site in the bcl-2 promoter appears to play a major role in the induction of bcl-2 expression during the activation of mature B cells and during the rescue of immature B cells from apoptosis. It is possible that the CRE site is responsible for induction of bcl-2 expression in other cell types, particularly those in which protein kinase C is involved. "
],
"offsets": [
[
0,
2323
]
]
}
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13,
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]
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],
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2227,
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]
],
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},
{
"id": "8816467_T24",
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"promoter"
],
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909,
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]
],
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},
{
"id": "8816467_T37",
"type": "Entity",
"text": [
"CRE site"
],
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[
1967,
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]
],
"normalized": []
}
] | [
{
"id": "8816467_E1",
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0,
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"role": "Theme",
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256,
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]
]
},
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"role": "Theme",
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]
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]
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"role": "Theme",
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"cross-linking"
],
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]
]
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]
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"role": "Theme",
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"loss"
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]
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"role": "Theme",
"ref_id": "8816467_E12"
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"functional activity"
],
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]
]
},
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"role": "Theme",
"ref_id": "8816467_T4"
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"role": "Site",
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}
]
},
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"id": "8816467_E13",
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"regulation"
],
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]
},
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"role": "Theme",
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}
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},
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"expression"
],
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]
]
},
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"role": "Theme",
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]
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"role": "Theme",
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"role": "Theme",
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},
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"id": "8816467_E17",
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"text": [
"mediated"
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"role": "Theme",
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]
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"role": "Theme",
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}
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},
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"type": "Positive_regulation",
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"text": [
"increased"
],
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1442,
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]
]
},
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"role": "Theme",
"ref_id": "8816467_E18"
}
]
},
{
"id": "8816467_E20",
"type": "Positive_regulation",
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"text": [
"dependent"
],
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]
},
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"role": "Theme",
"ref_id": "8816467_E18"
}
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},
{
"id": "8816467_E21",
"type": "Positive_regulation",
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"text": [
"necessary"
],
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1754,
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]
]
},
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{
"role": "Theme",
"ref_id": "8816467_E22"
}
]
},
{
"id": "8816467_E22",
"type": "Positive_regulation",
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"text": [
"optimal induction"
],
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1765,
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]
]
},
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"role": "Theme",
"ref_id": "8816467_E23"
}
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},
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"id": "8816467_E23",
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"expression"
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]
]
},
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"role": "Theme",
"ref_id": "8816467_T9"
}
]
},
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"id": "8816467_E24",
"type": "Positive_regulation",
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"text": [
"requires"
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]
]
},
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"role": "Theme",
"ref_id": "8816467_E22"
}
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},
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2022,
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]
]
},
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"role": "Theme",
"ref_id": "8816467_E26"
},
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"role": "Cause",
"ref_id": "8816467_T10"
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"role": "CSite",
"ref_id": "8816467_T37"
}
]
},
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"induction"
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]
},
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"role": "Theme",
"ref_id": "8816467_E27"
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},
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"expression"
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2053,
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"role": "Theme",
"ref_id": "8816467_T11"
}
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},
{
"id": "8816467_E28",
"type": "Regulation",
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"text": [
"responsible"
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2198,
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]
]
},
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"role": "Theme",
"ref_id": "8816467_E29"
}
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},
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"induction"
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"role": "Theme",
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"expression"
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"role": "Theme",
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},
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"id": "8816467_E31",
"type": "Regulation",
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"text": [
"involved"
],
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2313,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8816467_E28"
}
]
}
] | [] | [] |
9730957 | 9730957 | [
{
"id": "9730957__text",
"type": "abstract",
"text": [
"Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin. \nEndotoxin selectively induces monocyte Mn superoxide dismutase (SOD) without affecting levels of Cu,Zn SOD, catalase, or glutathione peroxidase. However, little is known about the structure-activity relationship and the mechanism by which endotoxin induces Mn SOD. In this study we demonstrated that a mutant Escherichia coli endotoxin lacking myristoyl fatty acid at the 3' R-3-hydroxymyristate position of the lipid A moiety retained its full capacity to coagulate Limulus amoebocyte lysate compared with the wild-type E. coli endotoxin and markedly stimulated the activation of human monocyte nuclear factor-kappaB and the induction of Mn SOD mRNA and enzyme activity. However, in contrast to the wild-type endotoxin, it failed to induce significant production of tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha by monocytes and did not induce the phosphorylation and nuclear translocation of mitogen-activated protein kinase. These results suggest that 1) lipid A myristoyl fatty acid, although it is important for the induction of inflammatory cytokine production by human monocytes, is not necessary for the induction of Mn SOD, 2) endotoxin-mediated induction of Mn SOD and inflammatory cytokines are regulated, at least in part, through different signal transduction pathways, and 3) failure of the mutant endotoxin to induce tumor necrosis factor-alpha production is, at least in part, due to its inability to activate mitogen-activated protein kinase. "
],
"offsets": [
[
0,
1589
]
]
}
] | [
{
"id": "9730957_T1",
"type": "Protein",
"text": [
"Mn SOD"
],
"offsets": [
[
13,
19
]
],
"normalized": []
},
{
"id": "9730957_T2",
"type": "Protein",
"text": [
"Mn superoxide dismutase"
],
"offsets": [
[
143,
166
]
],
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},
{
"id": "9730957_T3",
"type": "Protein",
"text": [
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],
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201,
210
]
],
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},
{
"id": "9730957_T4",
"type": "Protein",
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],
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212,
220
]
],
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},
{
"id": "9730957_T5",
"type": "Protein",
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],
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361,
367
]
],
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},
{
"id": "9730957_T6",
"type": "Protein",
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],
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743,
749
]
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},
{
"id": "9730957_T7",
"type": "Protein",
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],
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871,
898
]
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},
{
"id": "9730957_T8",
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],
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903,
941
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},
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"id": "9730957_T9",
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1254,
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"id": "9730957_T10",
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],
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1297,
1303
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"id": "9730957_T11",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
1461,
1488
]
],
"normalized": []
}
] | [
{
"id": "9730957_E1",
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"Induction"
],
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[
0,
9
]
]
},
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"role": "Theme",
"ref_id": "9730957_T1"
}
]
},
{
"id": "9730957_E2",
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"text": [
"induces"
],
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126,
133
]
]
},
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"role": "Theme",
"ref_id": "9730957_T2"
}
]
},
{
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"affecting"
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181,
190
]
]
},
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"role": "Theme",
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}
]
},
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"type": "Regulation",
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"affecting"
],
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181,
190
]
]
},
"arguments": [
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"role": "Theme",
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}
]
},
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353,
360
]
]
},
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"role": "Theme",
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}
]
},
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"id": "9730957_E6",
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"stimulated"
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656,
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]
]
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"role": "Theme",
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]
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"role": "Theme",
"ref_id": "9730957_T6"
}
]
},
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"induce"
],
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838,
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]
]
},
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"role": "Theme",
"ref_id": "9730957_E11"
}
]
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"text": [
"induce"
],
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838,
844
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9730957_E10"
}
]
},
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"id": "9730957_E10",
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"production"
],
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]
]
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"arguments": [
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"role": "Theme",
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}
]
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"production"
],
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]
]
},
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"role": "Theme",
"ref_id": "9730957_T7"
}
]
},
{
"id": "9730957_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"necessary"
],
"offsets": [
[
1223,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9730957_E13"
}
]
},
{
"id": "9730957_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
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1241,
1250
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "9730957_T9"
}
]
},
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"id": "9730957_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1284,
1293
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9730957_T10"
}
]
},
{
"id": "9730957_E15",
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"trigger": {
"text": [
"regulated"
],
"offsets": [
[
1335,
1344
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9730957_E14"
}
]
},
{
"id": "9730957_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
1454,
1460
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9730957_E17"
}
]
},
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"id": "9730957_E17",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
1489,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9730957_T11"
}
]
},
{
"id": "9730957_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"due"
],
"offsets": [
[
1522,
1525
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9730957_E16"
}
]
}
] | [] | [] |
8692924 | 8692924 | [
{
"id": "8692924__text",
"type": "abstract",
"text": [
"BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. \nApproximately 40% of diffuse large cell lymphoma are associated with chromosomal translocations that deregulate the expression of the BCL6 gene by juxtaposing heterologous promoters to the BCL-6 coding domain. The BCL6 gene encodes a 95-kDa protein containing six C-terminal zinc-finger motifs and an N-terminal POZ domain, suggesting that it may function as a transcription factor. By using a DNA sequence selected for its ability to bind recombinant BCL-6 in vitro, we show here that BCL-6 is present in DNA-binding complexes in nuclear extracts from various B-cell lines. In transient transfectin experiments, BCL6 can repress transcription from promoters linked to its DNA target sequence and this activity is dependent upon specific DNA-binding and the presence of an intact N-terminal half of the protein. We demonstrate that this part of the BCL6 molecule contains an autonomous transrepressor domain and that two noncontiguous regions, including the POZ motif, mediate maximum transrepressive activity. These results indicate that the BCL-6 protein can function as a sequence-specific transcriptional repressor and have implications for the role of BCL6 in normal lymphoid development and lymphomagenesis. "
],
"offsets": [
[
0,
1299
]
]
}
] | [
{
"id": "8692924_T1",
"type": "Protein",
"text": [
"BCL-6"
],
"offsets": [
[
0,
5
]
],
"normalized": []
},
{
"id": "8692924_T2",
"type": "Protein",
"text": [
"BCL6"
],
"offsets": [
[
219,
223
]
],
"normalized": []
},
{
"id": "8692924_T3",
"type": "Protein",
"text": [
"BCL-6"
],
"offsets": [
[
274,
279
]
],
"normalized": []
},
{
"id": "8692924_T4",
"type": "Protein",
"text": [
"BCL6"
],
"offsets": [
[
299,
303
]
],
"normalized": []
},
{
"id": "8692924_T5",
"type": "Protein",
"text": [
"BCL-6"
],
"offsets": [
[
537,
542
]
],
"normalized": []
},
{
"id": "8692924_T6",
"type": "Protein",
"text": [
"BCL-6"
],
"offsets": [
[
571,
576
]
],
"normalized": []
},
{
"id": "8692924_T7",
"type": "Protein",
"text": [
"BCL6"
],
"offsets": [
[
698,
702
]
],
"normalized": []
},
{
"id": "8692924_T8",
"type": "Protein",
"text": [
"BCL6"
],
"offsets": [
[
934,
938
]
],
"normalized": []
},
{
"id": "8692924_T9",
"type": "Protein",
"text": [
"BCL-6"
],
"offsets": [
[
1128,
1133
]
],
"normalized": []
},
{
"id": "8692924_T10",
"type": "Protein",
"text": [
"BCL6"
],
"offsets": [
[
1242,
1246
]
],
"normalized": []
}
] | [
{
"id": "8692924_E1",
"type": "Regulation",
"trigger": {
"text": [
"deregulate"
],
"offsets": [
[
186,
196
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8692924_E2"
}
]
},
{
"id": "8692924_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
201,
211
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8692924_T2"
}
]
}
] | [] | [] |
7526398 | 7526398 | [
{
"id": "7526398__text",
"type": "abstract",
"text": [
"Separation of oxidant-initiated and redox-regulated steps in the NF-kappa B signal transduction pathway. \nStudies presented here show that overall NF-kappa B signal transduction begins with a parallel series of stimuli-specific pathways through which cytokines (tumor necrosis factor alpha), oxidants (hydrogen peroxide and mitomycin C), and phorbol ester (phorbol 12-myristate 13-acetate) individually initiate signaling. These initial pathways culminate in a common pathway through which all of the stimulating agents ultimately signal NF-kappa B activation. We distinguish the stimuli-specific pathways by showing that the oxidative stimuli trigger NF-kappa B activation in only one of two human T-cell lines (Wurzburg but not Jurkat), whereas tumor necrosis factor alpha and phorbol 12-myristate 13-acetate readily stimulate in both lines. We propose the common pathway as the simplest way of accounting for the common requirements and properties of the signaling pathway. We include a redox-regulatory mechanism(s) in this common pathway to account for the previously demonstrated redox regulation of NF-kappa B activation in Jurkat cells (in which oxidants don't activate NF-kappa B); we put tyrosine phosphorylation in the common pathway by showing that kinase activity (inhibitable by herbimycin A and tyrphostin 47) is required for NF-kappa B activation by all stimuli tested in both cell lines. Since internal sites of oxidant production have been shown to play a key role in the cytokine-stimulated activation of NF-kappa B, and since tyrosine kinase and phosphatase activities are known to be altered by oxidants, these findings suggest that intracellular redox status controls NF-kappa B activation by regulating tyrosine phosphorylation event(s) within the common step of the NF-kappa B signal transduction pathway. "
],
"offsets": [
[
0,
1830
]
]
}
] | [
{
"id": "7526398_T1",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
262,
289
]
],
"normalized": []
},
{
"id": "7526398_T2",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
747,
774
]
],
"normalized": []
}
] | [] | [] | [] |
8790376 | 8790376 | [
{
"id": "8790376__text",
"type": "abstract",
"text": [
"Activation of Stat 5b in erythroid progenitors correlates with the ability of ErbB to induce sustained cell proliferation. \nSelf renewal of normal erythroid progenitors is induced by the receptor tyrosine kinase c-ErbB, whereas other receptors (c-Kit/Epo-R) regulate erythroid differentiation. To address possible mechanisms that could explain this selective activity of c-ErbB, we analyzed the ability of these receptors to activate the different members of the Stat transcription factor family. Ligand activation of c-ErbB induced the tyrosine phosphorylation, DNA-binding, and reporter gene transcription of Stat 5b in erythroblasts. In contrast, ligand activation of c-Kit was unable to induce any of these effects in the same cells. Activation of the erythropoietin receptor caused specific DNA-binding of Stat 5b, but failed to induce reporter gene transcription. These biochemical findings correlate perfectly with the selective ability of c-ErbB to cause sustained self renewal in erythroid progenitors. "
],
"offsets": [
[
0,
1012
]
]
}
] | [
{
"id": "8790376_T1",
"type": "Protein",
"text": [
"Stat 5b"
],
"offsets": [
[
14,
21
]
],
"normalized": []
},
{
"id": "8790376_T2",
"type": "Protein",
"text": [
"c-Kit"
],
"offsets": [
[
245,
250
]
],
"normalized": []
},
{
"id": "8790376_T3",
"type": "Protein",
"text": [
"Epo-R"
],
"offsets": [
[
251,
256
]
],
"normalized": []
},
{
"id": "8790376_T4",
"type": "Protein",
"text": [
"Stat 5b"
],
"offsets": [
[
611,
618
]
],
"normalized": []
},
{
"id": "8790376_T5",
"type": "Protein",
"text": [
"c-Kit"
],
"offsets": [
[
671,
676
]
],
"normalized": []
},
{
"id": "8790376_T6",
"type": "Protein",
"text": [
"erythropoietin receptor"
],
"offsets": [
[
756,
779
]
],
"normalized": []
},
{
"id": "8790376_T7",
"type": "Protein",
"text": [
"Stat 5b"
],
"offsets": [
[
811,
818
]
],
"normalized": []
},
{
"id": "8790376_T10",
"type": "Entity",
"text": [
"tyrosine"
],
"offsets": [
[
537,
545
]
],
"normalized": []
}
] | [
{
"id": "8790376_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"Activation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_T1"
}
]
},
{
"id": "8790376_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
525,
532
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_E5"
}
]
},
{
"id": "8790376_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
525,
532
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_E4"
}
]
},
{
"id": "8790376_E4",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
546,
561
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_T4"
},
{
"role": "Site",
"ref_id": "8790376_T10"
}
]
},
{
"id": "8790376_E5",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
567,
574
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_T4"
}
]
},
{
"id": "8790376_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
657,
667
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_T5"
}
]
},
{
"id": "8790376_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
691,
697
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_E5"
},
{
"role": "Cause",
"ref_id": "8790376_E6"
}
]
},
{
"id": "8790376_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
691,
697
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_E4"
},
{
"role": "Cause",
"ref_id": "8790376_E6"
}
]
},
{
"id": "8790376_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"Activation"
],
"offsets": [
[
738,
748
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_T6"
}
]
},
{
"id": "8790376_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"caused"
],
"offsets": [
[
780,
786
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_E11"
},
{
"role": "Cause",
"ref_id": "8790376_E9"
}
]
},
{
"id": "8790376_E11",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
800,
807
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8790376_T7"
}
]
}
] | [] | [] |
9823774 | 9823774 | [
{
"id": "9823774__text",
"type": "abstract",
"text": [
"Granulocyte colony-stimulating factor activates a 72-kDa isoform of STAT3 in human neutrophils. \nGranulocyte colony-stimulating factor (G-CSF) signaling involves activation of STATs, proteins that serve the dual function of signal transduction and activation of transcription. We previously demonstrated that G-CSF activated a distinct Stat3-like protein in immature and mature normal myeloid cells, StatG. StatG in normal immature human myeloid cells, i.e. adult CD34+ bone marrow cells, was composed of Stat3beta. This investigation was undertaken to determine the composition of StatG in mature normal human myeloid cells, i.e. polymorphonuclear neutrophilic granulocytes (PMN). These studies revealed that the major protein in extracts of PMN activated by G-CSF to bind the high-affinity serum-inducible element (hSIE) is a 72-kDa protein that cross-reacts with Stat3 monoclonal antibody, which we have designated Stat3gamma. Stat3gamma is derived from Stat3alpha by limited proteolysis and lacks the carboxyl-terminal portion of Stat3alpha. Because this region of Stat3alpha is involved in transcriptional activation, our findings suggest the possibility that Stat3gamma may be transcriptionally inactive and may compete with Stat3alpha for Stat3 binding sites in these terminally differentiated myeloid cells. "
],
"offsets": [
[
0,
1316
]
]
}
] | [
{
"id": "9823774_T1",
"type": "Protein",
"text": [
"Granulocyte colony-stimulating factor"
],
"offsets": [
[
0,
37
]
],
"normalized": []
},
{
"id": "9823774_T2",
"type": "Protein",
"text": [
"STAT3"
],
"offsets": [
[
68,
73
]
],
"normalized": []
},
{
"id": "9823774_T3",
"type": "Protein",
"text": [
"Granulocyte colony-stimulating factor"
],
"offsets": [
[
97,
134
]
],
"normalized": []
},
{
"id": "9823774_T4",
"type": "Protein",
"text": [
"G-CSF"
],
"offsets": [
[
136,
141
]
],
"normalized": []
},
{
"id": "9823774_T5",
"type": "Protein",
"text": [
"G-CSF"
],
"offsets": [
[
309,
314
]
],
"normalized": []
},
{
"id": "9823774_T6",
"type": "Protein",
"text": [
"Stat3"
],
"offsets": [
[
336,
341
]
],
"normalized": []
},
{
"id": "9823774_T7",
"type": "Protein",
"text": [
"StatG"
],
"offsets": [
[
400,
405
]
],
"normalized": []
},
{
"id": "9823774_T8",
"type": "Protein",
"text": [
"StatG"
],
"offsets": [
[
407,
412
]
],
"normalized": []
},
{
"id": "9823774_T9",
"type": "Protein",
"text": [
"CD34"
],
"offsets": [
[
464,
468
]
],
"normalized": []
},
{
"id": "9823774_T10",
"type": "Protein",
"text": [
"Stat3beta"
],
"offsets": [
[
505,
514
]
],
"normalized": []
},
{
"id": "9823774_T11",
"type": "Protein",
"text": [
"StatG"
],
"offsets": [
[
582,
587
]
],
"normalized": []
},
{
"id": "9823774_T12",
"type": "Protein",
"text": [
"G-CSF"
],
"offsets": [
[
760,
765
]
],
"normalized": []
},
{
"id": "9823774_T13",
"type": "Protein",
"text": [
"Stat3"
],
"offsets": [
[
866,
871
]
],
"normalized": []
},
{
"id": "9823774_T14",
"type": "Protein",
"text": [
"Stat3gamma"
],
"offsets": [
[
918,
928
]
],
"normalized": []
},
{
"id": "9823774_T15",
"type": "Protein",
"text": [
"Stat3gamma"
],
"offsets": [
[
930,
940
]
],
"normalized": []
},
{
"id": "9823774_T16",
"type": "Protein",
"text": [
"Stat3alpha"
],
"offsets": [
[
957,
967
]
],
"normalized": []
},
{
"id": "9823774_T17",
"type": "Protein",
"text": [
"Stat3alpha"
],
"offsets": [
[
1034,
1044
]
],
"normalized": []
},
{
"id": "9823774_T18",
"type": "Protein",
"text": [
"Stat3alpha"
],
"offsets": [
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1069,
1079
]
],
"normalized": []
},
{
"id": "9823774_T19",
"type": "Protein",
"text": [
"Stat3gamma"
],
"offsets": [
[
1165,
1175
]
],
"normalized": []
},
{
"id": "9823774_T20",
"type": "Protein",
"text": [
"Stat3alpha"
],
"offsets": [
[
1231,
1241
]
],
"normalized": []
},
{
"id": "9823774_T21",
"type": "Protein",
"text": [
"Stat3"
],
"offsets": [
[
1246,
1251
]
],
"normalized": []
}
] | [
{
"id": "9823774_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
315,
324
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9823774_T7"
},
{
"role": "Cause",
"ref_id": "9823774_T5"
}
]
},
{
"id": "9823774_E2",
"type": "Binding",
"trigger": {
"text": [
"cross-reacts"
],
"offsets": [
[
848,
860
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9823774_T14"
}
]
},
{
"id": "9823774_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"derived"
],
"offsets": [
[
944,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9823774_T15"
},
{
"role": "Cause",
"ref_id": "9823774_E4"
}
]
},
{
"id": "9823774_E4",
"type": "Protein_catabolism",
"trigger": {
"text": [
"proteolysis"
],
"offsets": [
[
979,
990
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9823774_T16"
}
]
},
{
"id": "9823774_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"compete"
],
"offsets": [
[
1218,
1225
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9823774_T20"
}
]
},
{
"id": "9823774_E6",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1252,
1259
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9823774_T19"
}
]
},
{
"id": "9823774_E7",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1252,
1259
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9823774_T20"
}
]
}
] | [
{
"id": "9823774_1",
"entity_ids": [
"9823774_T3",
"9823774_T4"
]
}
] | [] |
9188842 | 9188842 | [
{
"id": "9188842__text",
"type": "abstract",
"text": [
"Concomitant downregulation of IgH 3' enhancer activity and c-myc expression in a plasmacytoma x fibroblast environment: implications for dysregulation of translocated c-myc. \nRegulation of immunoglobulin heavy chain (IgH) gene expression is controlled by a B cell-specific promoter, intronic enhancer and additional B cell-specific enhancer elements identified recently in the 3' end of the IgH locus. One of the latter elements, the IgH 3' enhancer, is of particular interest: (1) it is B cell-specific and active only in late B cell development; (2) in rodent plasmacytomas and in some human Burkitt's lymphomas it is part of a locus control region (LCR) that is involved in deregulation of the c-myc oncogene as a result of translocation into the IgH locus; and (3) it has been implicated in the mechanisms that control Ig gene class switch recombination. We have used a somatic cell hybridization approach to genetically analyse regulation of the activity of the IgH 3' enhancer. When mouse MPC11 plasmacytoma cells, in which the IgH 3' enhancer is active, are fused with fibroblasts, Ig expression is extinguished at the level of transcription. Here we show that in a MPC11 plasmacytoma x fibroblast environment, the IgH 3' enhancer is transcriptionally inactive. Furthermore, we demonstrate that binding of several B cell-specific transcription factors, essential for IgH 3' enhancer activity, is lacking, which may explain 3' enhancer inactivity, although the binding of repressors cannot be excluded. Moreover, the high expression level of c-myc, characteristic of the parental MPC11 cells carrying the t(12;15) translocation, is down-regulated in the hybrids to that in unfused fibroblasts. Therefore, inactivation of the IgH 3' enhancer is a multifactorial process affecting several transcription factors that control the cell-specific and developmental activity of the enhancer. "
],
"offsets": [
[
0,
1890
]
]
}
] | [
{
"id": "9188842_T1",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
59,
64
]
],
"normalized": []
},
{
"id": "9188842_T2",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
167,
172
]
],
"normalized": []
},
{
"id": "9188842_T3",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
697,
702
]
],
"normalized": []
},
{
"id": "9188842_T4",
"type": "Protein",
"text": [
"c-myc"
],
"offsets": [
[
1548,
1553
]
],
"normalized": []
},
{
"id": "9188842_T13",
"type": "Entity",
"text": [
"IgH locus"
],
"offsets": [
[
750,
759
]
],
"normalized": []
}
] | [
{
"id": "9188842_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"downregulation"
],
"offsets": [
[
12,
26
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_E2"
}
]
},
{
"id": "9188842_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
65,
75
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_T1"
}
]
},
{
"id": "9188842_E3",
"type": "Regulation",
"trigger": {
"text": [
"dysregulation"
],
"offsets": [
[
137,
150
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_E4"
}
]
},
{
"id": "9188842_E4",
"type": "Localization",
"trigger": {
"text": [
"translocated"
],
"offsets": [
[
154,
166
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_T2"
}
]
},
{
"id": "9188842_E5",
"type": "Regulation",
"trigger": {
"text": [
"involved"
],
"offsets": [
[
665,
673
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_E6"
}
]
},
{
"id": "9188842_E6",
"type": "Regulation",
"trigger": {
"text": [
"deregulation"
],
"offsets": [
[
677,
689
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_T3"
}
]
},
{
"id": "9188842_E7",
"type": "Regulation",
"trigger": {
"text": [
"result"
],
"offsets": [
[
717,
723
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_E6"
},
{
"role": "Cause",
"ref_id": "9188842_E8"
}
]
},
{
"id": "9188842_E8",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
727,
740
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_T3"
},
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"role": "ToLoc",
"ref_id": "9188842_T13"
}
]
},
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"id": "9188842_E9",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1528,
1538
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_T4"
}
]
},
{
"id": "9188842_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"down-regulated"
],
"offsets": [
[
1638,
1652
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9188842_E9"
}
]
}
] | [] | [] |
8162052 | 8162052 | [
{
"id": "8162052__text",
"type": "abstract",
"text": [
"Genes encoding general initiation factors for RNA polymerase II transcription are dispersed in the human genome. \nGeneral transcription factors are required for accurate initiation of transcription by RNA polymerase II. Human cDNAs encoding subunits of these factors have been cloned and sequenced. Using fluorescence in situ hybridization (FISH), we show here that the genes encoding the TATA-box binding protein (TBP), TFIIB, TFIIE alpha, TFIIE beta, RAP30, RAP74 and the 62 kDa subunit, of TFIIH are located at the human chromosomal bands 6q26-27, 1p21-22, 3q21-24, 8p12, 13q14, 19p13.3 and 11p14-15.1, respectively. This dispersed localization of a group of functionally related gene provides insights into the molecular mechanism of human genome evolution and their possible involvement in human diseases. "
],
"offsets": [
[
0,
811
]
]
}
] | [
{
"id": "8162052_T1",
"type": "Protein",
"text": [
"TATA-box binding protein"
],
"offsets": [
[
389,
413
]
],
"normalized": []
},
{
"id": "8162052_T2",
"type": "Protein",
"text": [
"TBP"
],
"offsets": [
[
415,
418
]
],
"normalized": []
},
{
"id": "8162052_T3",
"type": "Protein",
"text": [
"TFIIB"
],
"offsets": [
[
421,
426
]
],
"normalized": []
},
{
"id": "8162052_T4",
"type": "Protein",
"text": [
"TFIIE alpha"
],
"offsets": [
[
428,
439
]
],
"normalized": []
},
{
"id": "8162052_T5",
"type": "Protein",
"text": [
"TFIIE beta"
],
"offsets": [
[
441,
451
]
],
"normalized": []
},
{
"id": "8162052_T6",
"type": "Protein",
"text": [
"RAP30"
],
"offsets": [
[
453,
458
]
],
"normalized": []
},
{
"id": "8162052_T7",
"type": "Protein",
"text": [
"RAP74"
],
"offsets": [
[
460,
465
]
],
"normalized": []
}
] | [] | [
{
"id": "8162052_1",
"entity_ids": [
"8162052_T1",
"8162052_T2"
]
}
] | [] |
10023774 | 10023774 | [
{
"id": "10023774__text",
"type": "abstract",
"text": [
"RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes. \nRANTES (Regulated upon Activation, Normal T cell Expressed and Secreted) is a chemoattractant cytokine (chemokine) important in the generation of inflammatory infiltrate and human immunodeficiency virus entry into immune cells. RANTES is expressed late (3-5 days) after activation in T lymphocytes. Using expression cloning, we identified the first \"late\" T lymphocyte associated transcription factor and named it \"RANTES Factor of Late Activated T Lymphocytes-1\" (RFLAT-1). RFLAT-1 is a novel, phosphorylated, zinc finger transcription factor that is expressed in T cells 3 days after activation, coincident with RANTES expression. While Rel proteins play the dominant role in RANTES gene expression in fibroblasts, RFLAT-1 is a strong transactivator for RANTES in T cells. "
],
"offsets": [
[
0,
880
]
]
}
] | [
{
"id": "10023774_T1",
"type": "Protein",
"text": [
"RFLAT-1"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "10023774_T2",
"type": "Protein",
"text": [
"RANTES"
],
"offsets": [
[
63,
69
]
],
"normalized": []
},
{
"id": "10023774_T3",
"type": "Protein",
"text": [
"RANTES"
],
"offsets": [
[
105,
111
]
],
"normalized": []
},
{
"id": "10023774_T4",
"type": "Protein",
"text": [
"Regulated upon Activation, Normal T cell Expressed and Secreted"
],
"offsets": [
[
113,
176
]
],
"normalized": []
},
{
"id": "10023774_T5",
"type": "Protein",
"text": [
"RANTES"
],
"offsets": [
[
333,
339
]
],
"normalized": []
},
{
"id": "10023774_T6",
"type": "Protein",
"text": [
"RANTES Factor of Late Activated T Lymphocytes-1"
],
"offsets": [
[
520,
567
]
],
"normalized": []
},
{
"id": "10023774_T7",
"type": "Protein",
"text": [
"RFLAT-1"
],
"offsets": [
[
570,
577
]
],
"normalized": []
},
{
"id": "10023774_T8",
"type": "Protein",
"text": [
"RFLAT-1"
],
"offsets": [
[
580,
587
]
],
"normalized": []
},
{
"id": "10023774_T9",
"type": "Protein",
"text": [
"RANTES"
],
"offsets": [
[
719,
725
]
],
"normalized": []
},
{
"id": "10023774_T10",
"type": "Protein",
"text": [
"RANTES"
],
"offsets": [
[
783,
789
]
],
"normalized": []
},
{
"id": "10023774_T11",
"type": "Protein",
"text": [
"RFLAT-1"
],
"offsets": [
[
822,
829
]
],
"normalized": []
},
{
"id": "10023774_T12",
"type": "Protein",
"text": [
"RANTES"
],
"offsets": [
[
861,
867
]
],
"normalized": []
}
] | [
{
"id": "10023774_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activates"
],
"offsets": [
[
53,
62
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_E2"
},
{
"role": "Cause",
"ref_id": "10023774_T1"
}
]
},
{
"id": "10023774_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
75,
85
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_T2"
}
]
},
{
"id": "10023774_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
343,
352
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_T5"
}
]
},
{
"id": "10023774_E4",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
600,
614
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_T8"
}
]
},
{
"id": "10023774_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
657,
666
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_T8"
}
]
},
{
"id": "10023774_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
726,
736
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_T9"
}
]
},
{
"id": "10023774_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"dominant role"
],
"offsets": [
[
766,
779
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_E8"
}
]
},
{
"id": "10023774_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
795,
805
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_T10"
}
]
},
{
"id": "10023774_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivator"
],
"offsets": [
[
842,
856
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10023774_T12"
},
{
"role": "Cause",
"ref_id": "10023774_T11"
}
]
}
] | [
{
"id": "10023774_1",
"entity_ids": [
"10023774_T3",
"10023774_T4"
]
}
] | [] |
8051172 | 8051172 | [
{
"id": "8051172__text",
"type": "abstract",
"text": [
"ZAP-70 tyrosine kinase, CD45, and T cell receptor involvement in UV- and H2O2-induced T cell signal transduction. \nSeveral mammalian responses to UV irradiation, including the activation of NF-kappa B, are believed to involve tyrosine phosphorylation. UV irradiation and H2O2 treatment of T lymphocytes induce protein tyrosine phosphorylation and Ca2+ signals similar to those observed following biological stimulation. We have examined the role of cell surface molecules in these responses. Normal T lymphocytes whose surface expression of CD3 was depleted showed impaired UV-induced tyrosine phosphorylation and Ca2+ signals. Similarly, Jurkat T cell lines deficient in CD3 or CD45 expression also gave impaired UV responses. However, all these cell types still gave strong Ca2+ and tyrosine phosphorylation responses to H2O2. The T cell tyrosine kinase ZAP-70 was found to be highly responsive to UV and H2O2 treatment. ZAP-70 responsiveness to UV required expression of both CD3 and CD45, whereas only CD3 was required for the response to H2O2. UV-induced activation of NF-kappa B was blocked by CD3 depletion, indicating the importance of such cell surface molecules in biological responses to UV. In nonlymphoid cells, the epidermal growth factor receptor displayed increased tyrosine phosphorylation within seconds of UV irradiation. These results suggest that UV-induced signal transduction is mediated via cell surface receptors that normally respond to biological stimulation, whereas H2O2 is able to partially bypass this requirement. "
],
"offsets": [
[
0,
1546
]
]
}
] | [
{
"id": "8051172_T1",
"type": "Protein",
"text": [
"ZAP-70"
],
"offsets": [
[
0,
6
]
],
"normalized": []
},
{
"id": "8051172_T2",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
24,
28
]
],
"normalized": []
},
{
"id": "8051172_T3",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
679,
683
]
],
"normalized": []
},
{
"id": "8051172_T4",
"type": "Protein",
"text": [
"ZAP-70"
],
"offsets": [
[
856,
862
]
],
"normalized": []
},
{
"id": "8051172_T5",
"type": "Protein",
"text": [
"ZAP-70"
],
"offsets": [
[
923,
929
]
],
"normalized": []
},
{
"id": "8051172_T6",
"type": "Protein",
"text": [
"CD45"
],
"offsets": [
[
987,
991
]
],
"normalized": []
},
{
"id": "8051172_T7",
"type": "Protein",
"text": [
"epidermal growth factor receptor"
],
"offsets": [
[
1229,
1261
]
],
"normalized": []
},
{
"id": "8051172_T15",
"type": "Entity",
"text": [
"tyrosine"
],
"offsets": [
[
1282,
1290
]
],
"normalized": []
}
] | [
{
"id": "8051172_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"deficient"
],
"offsets": [
[
659,
668
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8051172_E2"
}
]
},
{
"id": "8051172_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
684,
694
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8051172_T3"
}
]
},
{
"id": "8051172_E3",
"type": "Regulation",
"trigger": {
"text": [
"responsive"
],
"offsets": [
[
886,
896
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8051172_T4"
}
]
},
{
"id": "8051172_E4",
"type": "Regulation",
"trigger": {
"text": [
"responsive"
],
"offsets": [
[
886,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8051172_T5"
}
]
},
{
"id": "8051172_E5",
"type": "Regulation",
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"text": [
"responsiveness"
],
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[
930,
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]
]
},
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{
"role": "Theme",
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}
]
},
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"id": "8051172_E6",
"type": "Gene_expression",
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"text": [
"expression"
],
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[
960,
970
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8051172_T6"
}
]
},
{
"id": "8051172_E7",
"type": "Regulation",
"trigger": {
"text": [
"response"
],
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[
1031,
1039
]
]
},
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{
"role": "Theme",
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}
]
},
{
"id": "8051172_E8",
"type": "Positive_regulation",
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"text": [
"increased"
],
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[
1272,
1281
]
]
},
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{
"role": "Theme",
"ref_id": "8051172_E9"
}
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},
{
"id": "8051172_E9",
"type": "Phosphorylation",
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"text": [
"phosphorylation"
],
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1291,
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]
]
},
"arguments": [
{
"role": "Theme",
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},
{
"role": "Site",
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}
]
}
] | [] | [] |
9819382 | 9819382 | [
{
"id": "9819382__text",
"type": "abstract",
"text": [
"TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3. \nPreviously, we have shown that TAL1 and the LIM-only protein gene (LMO) are regularly coactivated in T-cell acute lymphoblastic leukemia (T-ALL). This observation is likely to relate to the findings that TAL1 and LMO are highly synergistic in T-cell tumorigenesis in double-transgenic mice. To understand the molecular mechanisms of functional synergy between TAL1 and LMO in tumorigenesis and transcriptional regulation, we tried to identify downstream target genes regulated by TAL1 and LMO by a subtractive PCR method. One of the isolated genes, that for retinaldehyde dehydrogenase 2 (RALDH2), was regularly expressed in most of the T-ALL cell lines that coexpressed TAL1 and LMO. Exogenously transfected TAL1 and LMO, but not either alone, induced RALDH2 expression in a T-ALL cell line, HPB-ALL, not expressing endogeneous TAL1 or LMO. The RALDH2 transcripts in T-ALL were, however, mostly initiated within the second intron. Promoter analysis revealed that a GATA site in a cryptic promoter in the second intron was essential and sufficient for the TAL1- and LMO-dependent transcriptional activation, and GATA3 binds to this site. In addition, forced expression of GATA3 potentiated the induction of RALDH2 by TAL1 and LMO, and these three factors formed a complex in vivo. Furthermore, a TAL1 mutant not binding to DNA also activated the transcription of RALDH2 in the presence of LMO and GATA3. Collectively, we have identified the RALDH2 gene as a first example of direct transcriptional target genes regulated by TAL1 and LMO in T-ALL. In this case, TAL1 and LMO act as cofactors for GATA3 to activate the transcription of RALDH2. "
],
"offsets": [
[
0,
1807
]
]
}
] | [
{
"id": "9819382_T1",
"type": "Protein",
"text": [
"TAL1"
],
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[
0,
4
]
],
"normalized": []
},
{
"id": "9819382_T2",
"type": "Protein",
"text": [
"retinaldehyde dehydrogenase 2"
],
"offsets": [
[
50,
79
]
],
"normalized": []
},
{
"id": "9819382_T3",
"type": "Protein",
"text": [
"GATA3"
],
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[
157,
162
]
],
"normalized": []
},
{
"id": "9819382_T4",
"type": "Protein",
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"TAL1"
],
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196,
200
]
],
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{
"id": "9819382_T5",
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"TAL1"
],
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369,
373
]
],
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},
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"id": "9819382_T6",
"type": "Protein",
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"TAL1"
],
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[
525,
529
]
],
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},
{
"id": "9819382_T7",
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"TAL1"
],
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645,
649
]
],
"normalized": []
},
{
"id": "9819382_T8",
"type": "Protein",
"text": [
"retinaldehyde dehydrogenase 2"
],
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[
723,
752
]
],
"normalized": []
},
{
"id": "9819382_T9",
"type": "Protein",
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"RALDH2"
],
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[
754,
760
]
],
"normalized": []
},
{
"id": "9819382_T10",
"type": "Protein",
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"TAL1"
],
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[
836,
840
]
],
"normalized": []
},
{
"id": "9819382_T11",
"type": "Protein",
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"TAL1"
],
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[
874,
878
]
],
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},
{
"id": "9819382_T12",
"type": "Protein",
"text": [
"RALDH2"
],
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918,
924
]
],
"normalized": []
},
{
"id": "9819382_T13",
"type": "Protein",
"text": [
"TAL1"
],
"offsets": [
[
994,
998
]
],
"normalized": []
},
{
"id": "9819382_T14",
"type": "Protein",
"text": [
"RALDH2"
],
"offsets": [
[
1011,
1017
]
],
"normalized": []
},
{
"id": "9819382_T15",
"type": "Protein",
"text": [
"TAL1"
],
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[
1221,
1225
]
],
"normalized": []
},
{
"id": "9819382_T16",
"type": "Protein",
"text": [
"GATA3"
],
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[
1277,
1282
]
],
"normalized": []
},
{
"id": "9819382_T17",
"type": "Protein",
"text": [
"GATA3"
],
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[
1337,
1342
]
],
"normalized": []
},
{
"id": "9819382_T18",
"type": "Protein",
"text": [
"RALDH2"
],
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[
1372,
1378
]
],
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},
{
"id": "9819382_T19",
"type": "Protein",
"text": [
"TAL1"
],
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[
1382,
1386
]
],
"normalized": []
},
{
"id": "9819382_T20",
"type": "Protein",
"text": [
"TAL1"
],
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[
1461,
1465
]
],
"normalized": []
},
{
"id": "9819382_T21",
"type": "Protein",
"text": [
"RALDH2"
],
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[
1528,
1534
]
],
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},
{
"id": "9819382_T22",
"type": "Protein",
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"GATA3"
],
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[
1562,
1567
]
],
"normalized": []
},
{
"id": "9819382_T23",
"type": "Protein",
"text": [
"RALDH2"
],
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[
1606,
1612
]
],
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},
{
"id": "9819382_T24",
"type": "Protein",
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"TAL1"
],
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1689,
1693
]
],
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},
{
"id": "9819382_T25",
"type": "Protein",
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"TAL1"
],
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1726,
1730
]
],
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},
{
"id": "9819382_T26",
"type": "Protein",
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"GATA3"
],
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1760,
1765
]
],
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},
{
"id": "9819382_T27",
"type": "Protein",
"text": [
"RALDH2"
],
"offsets": [
[
1799,
1805
]
],
"normalized": []
}
] | [
{
"id": "9819382_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
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[
43,
49
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E2"
}
]
},
{
"id": "9819382_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
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[
80,
90
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T2"
}
]
},
{
"id": "9819382_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"coactivated"
],
"offsets": [
[
251,
262
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T4"
}
]
},
{
"id": "9819382_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
777,
786
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T9"
}
]
},
{
"id": "9819382_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpressed"
],
"offsets": [
[
824,
835
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T10"
}
]
},
{
"id": "9819382_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"transfected"
],
"offsets": [
[
862,
873
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E7"
}
]
},
{
"id": "9819382_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"transfected"
],
"offsets": [
[
862,
873
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T11"
}
]
},
{
"id": "9819382_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
910,
917
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E10"
},
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"role": "Cause",
"ref_id": "9819382_E6"
}
]
},
{
"id": "9819382_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
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910,
917
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E10"
}
]
},
{
"id": "9819382_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
925,
935
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T12"
}
]
},
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"id": "9819382_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"expressing"
],
"offsets": [
[
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981
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T13"
}
]
},
{
"id": "9819382_E12",
"type": "Transcription",
"trigger": {
"text": [
"initiated"
],
"offsets": [
[
1061,
1070
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T14"
}
]
},
{
"id": "9819382_E13",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
1283,
1288
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T16"
}
]
},
{
"id": "9819382_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"forced"
],
"offsets": [
[
1316,
1322
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E15"
}
]
},
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"id": "9819382_E15",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1323,
1333
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T17"
}
]
},
{
"id": "9819382_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"potentiated"
],
"offsets": [
[
1343,
1354
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E17"
},
{
"role": "Cause",
"ref_id": "9819382_E14"
}
]
},
{
"id": "9819382_E17",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1359,
1368
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T18"
},
{
"role": "Cause",
"ref_id": "9819382_T19"
}
]
},
{
"id": "9819382_E18",
"type": "Binding",
"trigger": {
"text": [
"formed a complex"
],
"offsets": [
[
1420,
1436
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T17"
},
{
"role": "Theme",
"ref_id": "9819382_T19"
}
]
},
{
"id": "9819382_E19",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1477,
1484
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T20"
}
]
},
{
"id": "9819382_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
1497,
1506
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E21"
},
{
"role": "Cause",
"ref_id": "9819382_T20"
}
]
},
{
"id": "9819382_E21",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
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[
1511,
1524
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T21"
}
]
},
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"id": "9819382_E22",
"type": "Positive_regulation",
"trigger": {
"text": [
"in the presence of"
],
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[
1535,
1553
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E20"
},
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"role": "Cause",
"ref_id": "9819382_T22"
}
]
},
{
"id": "9819382_E23",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
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[
1676,
1685
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T23"
},
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"role": "Cause",
"ref_id": "9819382_T24"
}
]
},
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"id": "9819382_E24",
"type": "Positive_regulation",
"trigger": {
"text": [
"activate"
],
"offsets": [
[
1769,
1777
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_E25"
}
]
},
{
"id": "9819382_E25",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1782,
1795
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9819382_T27"
}
]
}
] | [
{
"id": "9819382_1",
"entity_ids": [
"9819382_T8",
"9819382_T9"
]
}
] | [] |
8628295 | 8628295 | [
{
"id": "8628295__text",
"type": "abstract",
"text": [
"Role of EGR1 in regulation of stimulus-dependent CD44 transcription in B lymphocytes. \nThe immediate-early gene egr-1 encodes a transcription factor (EGR1) that links B-cell antigen receptor (BCR) signals to downstream activation events through the regulation of previously unidentified target genes. Here we identify the gene encoding the lymphocyte homing and migration protein CD44 as a target of EGR1 regulation in B cells. BCR-induced increases in CD44 mRNA expression and transcription levels are shown to occur in EGR1-expressing but not in nonexpressing subclones of the B-cell line WEHI-231. Kinetics of egr-1 transcription and the appearance of nuclear EGR1 protein precede CD44 induction and occur within 30 min after stimulation in the EGR1-expressing subclone. A single EGR1 binding motif is demonstrated at bp -301 of the human CD44 promoter. Cotransfection of a CD44 promoter-chloramphenicol acetyltransferase reporter construct with an egr-1 expression vector resulted in a 6.5- to 8.5-fold induction of transcriptional activity relative to an empty expression vector. The EGR1 binding motif was shown to be necessary for stimulus-induced expression of a CD44 promoter-chloramphenicol acetyltransferase reporter construct in nontransformed B lymphocytes and was required for transactivation by an EGR1 expression vector in a B-cell line. These studies identify EGR1 as an intermediary linking BCR-derived signals to the induction of CD44. The relevance of these molecular events to BCR signal transduction and antigen-stimulated B-cell-mediated immune responses is discussed. "
],
"offsets": [
[
0,
1592
]
]
}
] | [
{
"id": "8628295_T1",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
[
8,
12
]
],
"normalized": []
},
{
"id": "8628295_T2",
"type": "Protein",
"text": [
"CD44"
],
"offsets": [
[
49,
53
]
],
"normalized": []
},
{
"id": "8628295_T3",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
112,
117
]
],
"normalized": []
},
{
"id": "8628295_T4",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
[
150,
154
]
],
"normalized": []
},
{
"id": "8628295_T5",
"type": "Protein",
"text": [
"CD44"
],
"offsets": [
[
380,
384
]
],
"normalized": []
},
{
"id": "8628295_T6",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
[
400,
404
]
],
"normalized": []
},
{
"id": "8628295_T7",
"type": "Protein",
"text": [
"CD44"
],
"offsets": [
[
453,
457
]
],
"normalized": []
},
{
"id": "8628295_T8",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
[
521,
525
]
],
"normalized": []
},
{
"id": "8628295_T9",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
613,
618
]
],
"normalized": []
},
{
"id": "8628295_T10",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
[
663,
667
]
],
"normalized": []
},
{
"id": "8628295_T11",
"type": "Protein",
"text": [
"CD44"
],
"offsets": [
[
684,
688
]
],
"normalized": []
},
{
"id": "8628295_T12",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
[
748,
752
]
],
"normalized": []
},
{
"id": "8628295_T13",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
[
783,
787
]
],
"normalized": []
},
{
"id": "8628295_T14",
"type": "Protein",
"text": [
"CD44"
],
"offsets": [
[
842,
846
]
],
"normalized": []
},
{
"id": "8628295_T15",
"type": "Protein",
"text": [
"CD44"
],
"offsets": [
[
877,
881
]
],
"normalized": []
},
{
"id": "8628295_T16",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
"offsets": [
[
891,
924
]
],
"normalized": []
},
{
"id": "8628295_T17",
"type": "Protein",
"text": [
"egr-1"
],
"offsets": [
[
952,
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]
],
"normalized": []
},
{
"id": "8628295_T18",
"type": "Protein",
"text": [
"EGR1"
],
"offsets": [
[
1089,
1093
]
],
"normalized": []
},
{
"id": "8628295_T19",
"type": "Protein",
"text": [
"CD44"
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1171,
1175
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},
{
"id": "8628295_T20",
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],
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1185,
1218
]
],
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},
{
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],
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1313,
1317
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],
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{
"id": "8628295_T22",
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],
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1377,
1381
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{
"id": "8628295_T23",
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],
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1449,
1453
]
],
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},
{
"id": "8628295_T35",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
655,
662
]
],
"normalized": []
}
] | [
{
"id": "8628295_E1",
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"Role"
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0,
4
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},
{
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"regulation"
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16,
26
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8628295_E3"
}
]
},
{
"id": "8628295_E3",
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"trigger": {
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"dependent"
],
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39,
48
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8628295_E4"
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{
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54,
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}
]
},
{
"id": "8628295_E5",
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]
]
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},
{
"id": "8628295_E6",
"type": "Positive_regulation",
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"increases"
],
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440,
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]
]
},
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"role": "Theme",
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]
},
{
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]
]
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"role": "Theme",
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}
]
},
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]
]
},
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"role": "Theme",
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]
},
{
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"nonexpressing"
],
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548,
561
]
]
},
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"role": "Theme",
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},
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],
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]
]
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"role": "Theme",
"ref_id": "8628295_T10"
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}
]
},
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"id": "8628295_E12",
"type": "Positive_regulation",
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8628295_T11"
}
]
},
{
"id": "8628295_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"occur"
],
"offsets": [
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703,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8628295_E11"
}
]
},
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"id": "8628295_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"occur"
],
"offsets": [
[
703,
708
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8628295_E10"
}
]
},
{
"id": "8628295_E15",
"type": "Gene_expression",
"trigger": {
"text": [
"expressing"
],
"offsets": [
[
753,
763
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8628295_T12"
}
]
},
{
"id": "8628295_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"Cotransfection"
],
"offsets": [
[
857,
871
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8628295_E17"
}
]
},
{
"id": "8628295_E17",
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"text": [
"expression"
],
"offsets": [
[
958,
968
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8628295_T17"
}
]
},
{
"id": "8628295_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1007,
1016
]
]
},
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"role": "Theme",
"ref_id": "8628295_E19"
}
]
},
{
"id": "8628295_E19",
"type": "Transcription",
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"text": [
"transcriptional activity"
],
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1020,
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]
]
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"role": "Theme",
"ref_id": "8628295_T15"
}
]
},
{
"id": "8628295_E20",
"type": "Positive_regulation",
"trigger": {
"text": [
"intermediary linking"
],
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[
1388,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8628295_T22"
}
]
},
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"id": "8628295_E21",
"type": "Positive_regulation",
"trigger": {
"text": [
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],
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1388,
1408
]
]
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"role": "Theme",
"ref_id": "8628295_E22"
},
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"role": "Cause",
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}
]
},
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"id": "8628295_E22",
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],
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1436,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8628295_T23"
}
]
}
] | [] | [] |
9374467 | 9374467 | [
{
"id": "9374467__text",
"type": "abstract",
"text": [
"Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway. \nThe nuclear factor of activated T cells (NFAT) group of transcription factors is retained in the cytoplasm of quiescent cells. NFAT activation is mediated in part by induced nuclear import. This process requires calcium-dependent dephosphorylation of NFAT caused by the phosphatase calcineurin. The c-Jun amino-terminal kinase (JNK) phosphorylates NFAT4 on two sites. Mutational removal of the JNK phosphorylation sites caused constitutive nuclear localization of NFAT4. In contrast, JNK activation in calcineurin-stimulated cells caused nuclear exclusion of NFAT4. These findings show that the nuclear accumulation of NFAT4 promoted by calcineurin is opposed by the JNK signal transduction pathway. "
],
"offsets": [
[
0,
779
]
]
}
] | [
{
"id": "9374467_T1",
"type": "Protein",
"text": [
"NFAT4"
],
"offsets": [
[
24,
29
]
],
"normalized": []
},
{
"id": "9374467_T2",
"type": "Protein",
"text": [
"NFAT4"
],
"offsets": [
[
427,
432
]
],
"normalized": []
},
{
"id": "9374467_T3",
"type": "Protein",
"text": [
"NFAT4"
],
"offsets": [
[
543,
548
]
],
"normalized": []
},
{
"id": "9374467_T4",
"type": "Protein",
"text": [
"NFAT4"
],
"offsets": [
[
638,
643
]
],
"normalized": []
},
{
"id": "9374467_T5",
"type": "Protein",
"text": [
"NFAT4"
],
"offsets": [
[
698,
703
]
],
"normalized": []
},
{
"id": "9374467_T6",
"type": "Entity",
"text": [
"Nuclear"
],
"offsets": [
[
0,
7
]
],
"normalized": []
},
{
"id": "9374467_T11",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
519,
526
]
],
"normalized": []
},
{
"id": "9374467_T14",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
617,
624
]
],
"normalized": []
},
{
"id": "9374467_T16",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
674,
681
]
],
"normalized": []
}
] | [
{
"id": "9374467_E1",
"type": "Localization",
"trigger": {
"text": [
"accumulation"
],
"offsets": [
[
8,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9374467_T1"
},
{
"role": "AtLoc",
"ref_id": "9374467_T6"
}
]
},
{
"id": "9374467_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"opposed"
],
"offsets": [
[
30,
37
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9374467_E1"
}
]
},
{
"id": "9374467_E3",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylates"
],
"offsets": [
[
412,
426
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9374467_T2"
}
]
},
{
"id": "9374467_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"caused"
],
"offsets": [
[
499,
505
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9374467_E5"
}
]
},
{
"id": "9374467_E5",
"type": "Localization",
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"text": [
"localization"
],
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[
527,
539
]
]
},
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{
"role": "Theme",
"ref_id": "9374467_T3"
},
{
"role": "AtLoc",
"ref_id": "9374467_T11"
}
]
},
{
"id": "9374467_E6",
"type": "Positive_regulation",
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"text": [
"caused"
],
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[
610,
616
]
]
},
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"role": "Theme",
"ref_id": "9374467_E7"
}
]
},
{
"id": "9374467_E7",
"type": "Localization",
"trigger": {
"text": [
"exclusion"
],
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[
625,
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]
]
},
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"role": "Theme",
"ref_id": "9374467_T4"
},
{
"role": "AtLoc",
"ref_id": "9374467_T14"
}
]
},
{
"id": "9374467_E8",
"type": "Localization",
"trigger": {
"text": [
"accumulation"
],
"offsets": [
[
682,
694
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9374467_T5"
},
{
"role": "AtLoc",
"ref_id": "9374467_T16"
}
]
},
{
"id": "9374467_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"promoted"
],
"offsets": [
[
704,
712
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9374467_E8"
}
]
},
{
"id": "9374467_E10",
"type": "Negative_regulation",
"trigger": {
"text": [
"opposed"
],
"offsets": [
[
731,
738
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9374467_E9"
}
]
}
] | [] | [] |
7657825 | 7657825 | [
{
"id": "7657825__text",
"type": "abstract",
"text": [
"Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells. \nHTLV-1 infection causes an adult T cell leukemia in humans. The viral encoded protein tax, is thought to play an important role in oncogenesis. Our previous data obtained from a tax transgenic mouse model revealed that tax transforms mouse fibroblasts but not thymocytes, despite comparable levels of tax expression in both tissues. Constitutive tyrosine phosphorylation of a 130-kD protein(s) was observed in the tax transformed fibroblast B line and in HTLV-1 transformed human lymphoid lines, but not in thymocytes from Thy-tax transgenic mice. Phosphotyrosine immunoprecipitation followed by Western blot analysis with a set of Jak kinase specific antibodies, identified p130 as Jak2 in the tax transformed mouse fibroblastic cell line and Jak3 in HTLV-1 transformed human T cell lines. Phosphorylation of Jak2 in tax transformed cells resulted from high expression of IL-6. Tyrosine phosphorylation of this protein could also be induced in Balb/c3T3 cells using a supernatant from the B line, which was associated with induction of cell proliferation. Both phosphorylation and proliferation were inhibited by IL-6 neutralizing antibodies. Constitutive phosphorylation of Jak kinases may facilitate tumor growth in both HTLV-1 infected human T cells and the transgenic mouse model. "
],
"offsets": [
[
0,
1432
]
]
}
] | [
{
"id": "7657825_T1",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
105,
108
]
],
"normalized": []
},
{
"id": "7657825_T2",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
232,
235
]
],
"normalized": []
},
{
"id": "7657825_T3",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
324,
327
]
],
"normalized": []
},
{
"id": "7657825_T4",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
365,
368
]
],
"normalized": []
},
{
"id": "7657825_T5",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
447,
450
]
],
"normalized": []
},
{
"id": "7657825_T6",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
560,
563
]
],
"normalized": []
},
{
"id": "7657825_T7",
"type": "Protein",
"text": [
"Jak2"
],
"offsets": [
[
829,
833
]
],
"normalized": []
},
{
"id": "7657825_T8",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
841,
844
]
],
"normalized": []
},
{
"id": "7657825_T9",
"type": "Protein",
"text": [
"Jak3"
],
"offsets": [
[
890,
894
]
],
"normalized": []
},
{
"id": "7657825_T10",
"type": "Protein",
"text": [
"Jak2"
],
"offsets": [
[
956,
960
]
],
"normalized": []
},
{
"id": "7657825_T11",
"type": "Protein",
"text": [
"tax"
],
"offsets": [
[
964,
967
]
],
"normalized": []
},
{
"id": "7657825_T12",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1019,
1023
]
],
"normalized": []
},
{
"id": "7657825_T13",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1260,
1264
]
],
"normalized": []
},
{
"id": "7657825_T19",
"type": "Entity",
"text": [
"Tyrosine"
],
"offsets": [
[
1025,
1033
]
],
"normalized": []
}
] | [
{
"id": "7657825_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
451,
461
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7657825_T5"
}
]
},
{
"id": "7657825_E2",
"type": "Phosphorylation",
"trigger": {
"text": [
"Phosphorylation"
],
"offsets": [
[
937,
952
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7657825_T10"
}
]
},
{
"id": "7657825_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"resulted"
],
"offsets": [
[
986,
994
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7657825_E2"
},
{
"role": "Cause",
"ref_id": "7657825_E4"
}
]
},
{
"id": "7657825_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"high"
],
"offsets": [
[
1000,
1004
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7657825_E5"
}
]
},
{
"id": "7657825_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1005,
1015
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7657825_T12"
}
]
},
{
"id": "7657825_E6",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1034,
1049
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7657825_T10"
},
{
"role": "Site",
"ref_id": "7657825_T19"
}
]
},
{
"id": "7657825_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1080,
1087
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7657825_E6"
}
]
},
{
"id": "7657825_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1247,
1256
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7657825_E6"
}
]
}
] | [] | [] |
10232385 | 10232385 | [
{
"id": "10232385__text",
"type": "abstract",
"text": [
"Resistance to tumor necrosis factor induced apoptosis in vitro correlates with high metastatic capacity of cells in vivo. \nTNF is one of the cytokines secreted by the cells of the immune system. Our data demonstrate that those cell lines lacking capability to form metastatic tumors in vivo are susceptible to TNF induced apoptosis in vitro. However, cell lines with high metastatic potential are resistant to TNF in vitro. Furthermore, the same cell lines were resistant to cytolytic action of other cytotoxic proteins secreted by LAK cells. Our data showed that TNF resistance in vitro correlates with the increased level of transcription factor NF-kappaB. This finding may provide a tool to improve current protocols of immunotherapy and insights to how tumor cells are or are not killed by LAK cells. "
],
"offsets": [
[
0,
805
]
]
}
] | [] | [] | [] | [] |
9032280 | 9032280 | [
{
"id": "9032280__text",
"type": "abstract",
"text": [
"Transcription mediated by NFAT is highly inducible in effector CD4+ T helper 2 (Th2) cells but not in Th1 cells. \nTranscriptional factors of the NFAT family play an important role in regulating the expression of several cytokine genes during the immune response, such as the genes for interleukin 2 (IL-2) and IL-4, among others. Upon antigen stimulation, precursor CD4+ T helper (pTh) cells proliferate and differentiate into two populations of effector cells (eTh1 and eTh2), each one expressing a specific pattern of cytokines that distinguishes them from their precursors. eTh2 cells are the major source of IL-4, while gamma interferon is produced by eTh1 cells. Here we have used reporter transgenic mice to show that DNA binding and transcriptional activities of NFAT are transiently induced during the differentiation of pTh cells into either eTh1 or eTh2 cells to mediate the expression of IL-2 as a common growth factor in both pathways. However, although NFAT DNA binding is similarly induced in both eTh1 and eTh2 cells upon antigen stimulation, only the NFAT complexes present in eTh2 cells are able to mediate high-level transcription, and relatively little NFAT transcriptional activity was induced in eTh1 cells. In contrast to activated pTh cells, neither eTh1 nor eTh2 cells produced significant IL-2 upon stimulation, but the high levels of NFAT transcriptional activities directly correlate with the IL-4 production induced in response to antigen stimulation in eTh2 cells. These data suggest that activated NFAT is involved in the effector function of eTh2 cells and that the failure of eTh1 cells to produce IL-4 in response to an antigen is due, at least partially, to a failure to induce high-level transcription of the IL-4 gene by NFAT. Regulation of NFAT could be therefore a critical element in the polarization to eTh1 or eTh2. "
],
"offsets": [
[
0,
1857
]
]
}
] | [
{
"id": "9032280_T1",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
63,
66
]
],
"normalized": []
},
{
"id": "9032280_T2",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
285,
298
]
],
"normalized": []
},
{
"id": "9032280_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
300,
304
]
],
"normalized": []
},
{
"id": "9032280_T4",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
310,
314
]
],
"normalized": []
},
{
"id": "9032280_T5",
"type": "Protein",
"text": [
"CD4"
],
"offsets": [
[
366,
369
]
],
"normalized": []
},
{
"id": "9032280_T6",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
612,
616
]
],
"normalized": []
},
{
"id": "9032280_T7",
"type": "Protein",
"text": [
"gamma interferon"
],
"offsets": [
[
624,
640
]
],
"normalized": []
},
{
"id": "9032280_T8",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
899,
903
]
],
"normalized": []
},
{
"id": "9032280_T9",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1314,
1318
]
],
"normalized": []
},
{
"id": "9032280_T10",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1420,
1424
]
],
"normalized": []
},
{
"id": "9032280_T11",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1630,
1634
]
],
"normalized": []
},
{
"id": "9032280_T12",
"type": "Protein",
"text": [
"IL-4"
],
"offsets": [
[
1744,
1748
]
],
"normalized": []
}
] | [
{
"id": "9032280_E1",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
175,
179
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E4"
}
]
},
{
"id": "9032280_E2",
"type": "Regulation",
"trigger": {
"text": [
"role"
],
"offsets": [
[
175,
179
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E3"
}
]
},
{
"id": "9032280_E3",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
183,
193
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E6"
}
]
},
{
"id": "9032280_E4",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
183,
193
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E5"
}
]
},
{
"id": "9032280_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
198,
208
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T3"
}
]
},
{
"id": "9032280_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
198,
208
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T4"
}
]
},
{
"id": "9032280_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"source"
],
"offsets": [
[
602,
608
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T6"
}
]
},
{
"id": "9032280_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"produced"
],
"offsets": [
[
644,
652
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T7"
}
]
},
{
"id": "9032280_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediate"
],
"offsets": [
[
873,
880
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E10"
}
]
},
{
"id": "9032280_E10",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
885,
895
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T8"
}
]
},
{
"id": "9032280_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"produced"
],
"offsets": [
[
1293,
1301
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T9"
}
]
},
{
"id": "9032280_E12",
"type": "Gene_expression",
"trigger": {
"text": [
"production"
],
"offsets": [
[
1425,
1435
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T10"
}
]
},
{
"id": "9032280_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
1436,
1443
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E12"
}
]
},
{
"id": "9032280_E14",
"type": "Negative_regulation",
"trigger": {
"text": [
"failure"
],
"offsets": [
[
1597,
1604
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E16"
}
]
},
{
"id": "9032280_E15",
"type": "Gene_expression",
"trigger": {
"text": [
"produce"
],
"offsets": [
[
1622,
1629
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T11"
}
]
},
{
"id": "9032280_E16",
"type": "Regulation",
"trigger": {
"text": [
"in response to"
],
"offsets": [
[
1635,
1649
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E15"
}
]
},
{
"id": "9032280_E17",
"type": "Negative_regulation",
"trigger": {
"text": [
"failure"
],
"offsets": [
[
1694,
1701
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E18"
},
{
"role": "Cause",
"ref_id": "9032280_E14"
}
]
},
{
"id": "9032280_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
1705,
1711
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_E19"
}
]
},
{
"id": "9032280_E19",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
1723,
1736
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9032280_T12"
}
]
}
] | [
{
"id": "9032280_1",
"entity_ids": [
"9032280_T2",
"9032280_T3"
]
}
] | [] |
7637809 | 7637809 | [
{
"id": "7637809__text",
"type": "abstract",
"text": [
"An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes. \nLymphocytes are particularly susceptible to DNA damage-induced apoptosis, a response which may serve as a form of 'altruistic suicide' to counter their intrinsic high potential for mutation and clonal expansion. The tumour suppressor p53 has been shown to regulate this type of apoptosis in thymocytes, but an as yet unknown, p53-independent pathway(s) appears to mediate the same event in mitogen-activated mature T lymphocytes. Here we show DNA damage-induced apoptosis in these T lymphocytes is dependent on the antioncogenic transcription factor interferon regulatory factor (IRF)-1. Thus two different anti-onco-genic transcription factors, p53 and IRF-1, are required for distinct apoptotic pathways in T lymphocytes. We also show that mitogen induction of the interleukin-1 beta converting enzyme (ICE) gene, a mammalian homologue of the Caenorhabditis elegans cell death gene ced-3, is IRF-1-dependent. Ectopic overexpression of IRF-1 results in the activation of the endogenous gene for ICE and enhances the sensitivity of cells to radiation-induced apoptosis. "
],
"offsets": [
[
0,
1166
]
]
}
] | [
{
"id": "7637809_T1",
"type": "Protein",
"text": [
"IRF-1"
],
"offsets": [
[
3,
8
]
],
"normalized": []
},
{
"id": "7637809_T2",
"type": "Protein",
"text": [
"p53"
],
"offsets": [
[
330,
333
]
],
"normalized": []
},
{
"id": "7637809_T3",
"type": "Protein",
"text": [
"p53"
],
"offsets": [
[
422,
425
]
],
"normalized": []
},
{
"id": "7637809_T4",
"type": "Protein",
"text": [
"interferon regulatory factor (IRF)-1"
],
"offsets": [
[
646,
682
]
],
"normalized": []
},
{
"id": "7637809_T5",
"type": "Protein",
"text": [
"p53"
],
"offsets": [
[
742,
745
]
],
"normalized": []
},
{
"id": "7637809_T6",
"type": "Protein",
"text": [
"IRF-1"
],
"offsets": [
[
750,
755
]
],
"normalized": []
},
{
"id": "7637809_T7",
"type": "Protein",
"text": [
"interleukin-1 beta converting enzyme"
],
"offsets": [
[
863,
899
]
],
"normalized": []
},
{
"id": "7637809_T8",
"type": "Protein",
"text": [
"ICE"
],
"offsets": [
[
901,
904
]
],
"normalized": []
},
{
"id": "7637809_T9",
"type": "Protein",
"text": [
"ced-3"
],
"offsets": [
[
980,
985
]
],
"normalized": []
},
{
"id": "7637809_T10",
"type": "Protein",
"text": [
"IRF-1"
],
"offsets": [
[
990,
995
]
],
"normalized": []
},
{
"id": "7637809_T11",
"type": "Protein",
"text": [
"IRF-1"
],
"offsets": [
[
1033,
1038
]
],
"normalized": []
},
{
"id": "7637809_T12",
"type": "Protein",
"text": [
"ICE"
],
"offsets": [
[
1092,
1095
]
],
"normalized": []
}
] | [
{
"id": "7637809_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
846,
855
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7637809_T8"
}
]
},
{
"id": "7637809_E2",
"type": "Regulation",
"trigger": {
"text": [
"dependent"
],
"offsets": [
[
996,
1005
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7637809_E1"
},
{
"role": "Cause",
"ref_id": "7637809_T10"
}
]
},
{
"id": "7637809_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
1015,
1029
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7637809_T11"
}
]
},
{
"id": "7637809_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
1015,
1029
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7637809_E3"
}
]
},
{
"id": "7637809_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"results"
],
"offsets": [
[
1039,
1046
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7637809_E6"
},
{
"role": "Cause",
"ref_id": "7637809_E4"
}
]
},
{
"id": "7637809_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
"offsets": [
[
1054,
1064
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7637809_T12"
}
]
}
] | [
{
"id": "7637809_1",
"entity_ids": [
"7637809_T7",
"7637809_T8"
]
}
] | [] |
9765256 | 9765256 | [
{
"id": "9765256__text",
"type": "abstract",
"text": [
"Prostaglandin E2 Up-regulates HIV-1 long terminal repeat-driven gene activity in T cells via NF-kappaB-dependent and -independent signaling pathways. \nReplication of human immunodeficiency virus type-1 (HIV-1) is highly dependent on the state of activation of the infected cells and is modulated by interactions between viral and host cellular factors. Prostaglandin E2 (PGE2), a pleiotropic immunomodulatory molecule, is observed at elevated levels during HIV-1 infection as well as during the course of other pathogenic infections. In 1G5, a Jurkat-derived T cell line stably transfected with a luciferase gene driven by HIV-1 long terminal repeat (LTR), we found that PGE2 markedly enhanced HIV-1 LTR-mediated reporter gene activity. Experiments have been conducted to identify second messengers involved in this PGE2-dependent up-regulating effect on the regulatory element of HIV-1. In this study, we present evidence indicating that signal transduction pathways induced by PGE2 necessitate the participation of cyclic AMP, protein kinase A, and Ca2+. Experiments conducted with different HIV-1 LTR-based vectors suggested that PGE2-mediated activation effect on HIV-1 transcription was transduced via both NF-kappaB-dependent and -independent signaling pathways. The involvement of NF-kappaB in the PGE2-dependent activating effect on HIV-1 transcription was further confirmed using a kappaB-regulated luciferase encoding vector and by electrophoretic mobility shift assays. Results from Northern blot and flow cytometric analyses, as well as the use of a selective antagonist indicated that PGE2 modulation of HIV-1 LTR-driven reporter gene activity in studied T lymphoid cells is transduced via the EP4 receptor subtype. These results suggest that secretion of PGE2 by macrophages in response to infection or inflammatory activators could induce signaling events resulting in activation of proviral DNA present into T cells latently infected with HIV-1. "
],
"offsets": [
[
0,
1962
]
]
}
] | [
{
"id": "9765256_T1",
"type": "Protein",
"text": [
"EP4 receptor subtype"
],
"offsets": [
[
1707,
1727
]
],
"normalized": []
}
] | [] | [] | [] |
9271588 | 9271588 | [
{
"id": "9271588__text",
"type": "abstract",
"text": [
"Epstein-Barr virus binding to CD21 activates the initial viral promoter via NF-kappaB induction. \nEpstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects normal human B lymphocytes via CD21, the CR2 complement receptor. Studies of the mechanisms that enable EBV to infect nonactivated, noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor, which, in turn, binds to and mediates transcriptional activation of Wp, the initial viral latent gene promoter. Thus, EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB-dependent intracellular signaling pathway which is required for infection. "
],
"offsets": [
[
0,
769
]
]
}
] | [
{
"id": "9271588_T1",
"type": "Protein",
"text": [
"CD21"
],
"offsets": [
[
30,
34
]
],
"normalized": []
},
{
"id": "9271588_T2",
"type": "Protein",
"text": [
"CD21"
],
"offsets": [
[
208,
212
]
],
"normalized": []
},
{
"id": "9271588_T3",
"type": "Protein",
"text": [
"CR2"
],
"offsets": [
[
218,
221
]
],
"normalized": []
},
{
"id": "9271588_T4",
"type": "Protein",
"text": [
"CD21"
],
"offsets": [
[
405,
409
]
],
"normalized": []
}
] | [] | [] | [] |
8014029 | 8014029 | [
{
"id": "8014029__text",
"type": "abstract",
"text": [
"Increased interleukin 2 transcription in murine lymphocytes by ciprofloxacin. \nThe fluoroquinolone antibiotic, ciprofloxacin (cipro), induces hyperproduction of interleukin 2 (IL-2) and interferon-gamma (IFN-gamma) in stimulated human peripheral blood lymphocytes. In this investigation an enhanced and prolonged IL-2 and IL-2 mRNA response was also detected in both stimulated (T cell mitogens or alloantigens) murine splenocytes and in the stimulated murine T cell line EL-4 in the presence of ciprofloxacin (5-80 micrograms/ml) as compared to control cells without antibiotics. However, in contrast to human lymphocytes, IFN-gamma production was inhibited and IFN-gamma mRNA levels were unaffected at 24 h and only slightly upregulated at 48 and 72 h of culture in murine splenocytes incubated with cipro (20 micrograms/ml). EL-4 cells were transfected with a plasmid containing the IL-2 promoter and enhancer region linked to the chloramphenicol acetyltransferase (CAT) reporter gene. Analysis of CAT activity revealed that cipro enhanced IL-2 gene induction. In addition, EL-4 cells incubated with ciprofloxacin showed an early peak and more activated nuclear factor of activated T cells (NFAT-1) as compared to control cells without antibiotics. Cipro did not affect the nuclear transcription factors AP-1 or NFIL-2A. Taken together, cipro inhibited IFN-gamma synthesis, but enhanced IL-2 production in murine lymphocytes by means of influencing NFAT-1 and causing an increased IL-2 transcription. "
],
"offsets": [
[
0,
1504
]
]
}
] | [
{
"id": "8014029_T1",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
10,
23
]
],
"normalized": []
},
{
"id": "8014029_T2",
"type": "Protein",
"text": [
"interleukin 2"
],
"offsets": [
[
161,
174
]
],
"normalized": []
},
{
"id": "8014029_T3",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
176,
180
]
],
"normalized": []
},
{
"id": "8014029_T4",
"type": "Protein",
"text": [
"interferon-gamma"
],
"offsets": [
[
186,
202
]
],
"normalized": []
},
{
"id": "8014029_T5",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
204,
213
]
],
"normalized": []
},
{
"id": "8014029_T6",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
313,
317
]
],
"normalized": []
},
{
"id": "8014029_T7",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
322,
326
]
],
"normalized": []
},
{
"id": "8014029_T8",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
624,
633
]
],
"normalized": []
},
{
"id": "8014029_T9",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
663,
672
]
],
"normalized": []
},
{
"id": "8014029_T10",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
886,
890
]
],
"normalized": []
},
{
"id": "8014029_T11",
"type": "Protein",
"text": [
"chloramphenicol acetyltransferase"
],
"offsets": [
[
934,
967
]
],
"normalized": []
},
{
"id": "8014029_T12",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
969,
972
]
],
"normalized": []
},
{
"id": "8014029_T13",
"type": "Protein",
"text": [
"CAT"
],
"offsets": [
[
1001,
1004
]
],
"normalized": []
},
{
"id": "8014029_T14",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1043,
1047
]
],
"normalized": []
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{
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]
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{
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] | [] |
9020049 | 9020049 | [
{
"id": "9020049__text",
"type": "abstract",
"text": [
"Differentiation-dependent expression of a human carboxylesterase in monocytic cells and transcription factor binding to the promoter. \nCarboxylesterases play an important role in defense and clearance mechanisms of the monocyte/macrophage system. During the differentiation process of cells from the monocytic cell line THP-1 we observed a transient transcriptional upregulation of a human carboxylesterase analyzed by means of Northern blots. In PMA-treated THP-1 cells we could detect three major transcription initiation sites as revealed by Nuclease Protection Assay carried out with two overlapping antisense RNA probes. We have recently cloned the carboxylesterase upstream sequence and showed its basal promoter activity in CHO cells. Using electrophoretic mobility shift analysis we demonstrated that the promoter region spanning base pairs -1 to -275, which contains several putative binding sites for transcription factors, is bound by nuclear factors Sp1 and IRBP but not by C/EBPs. Taken together these data indicate that carboxylesterase gene transcription in THP-1 cells starts at multiple initiation sites and that Sp1 and IRBP may be critical factors for modulating the differentiation-dependent transcription of this human carboxylesterase gene. "
],
"offsets": [
[
0,
1263
]
]
}
] | [
{
"id": "9020049_T1",
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"Sp1"
],
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]
],
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{
"id": "9020049_T2",
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"IRBP"
],
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{
"id": "9020049_T3",
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"Sp1"
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"id": "9020049_T4",
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"IRBP"
],
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1138,
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]
],
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}
] | [
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"id": "9020049_E1",
"type": "Binding",
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"bound"
],
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}
] | [] | [] |
9464836 | 9464836 | [
{
"id": "9464836__text",
"type": "abstract",
"text": [
"Induction of interleukin-12 p40 transcript by CD40 ligation via activation of nuclear factor-kappaB. \nInterleukin-12 is produced in response to infection with bacteria or parasites or to bacterial constituents such as LPS in monocytes/macrophages and dendritic cells, and also generated by the interaction between activated T cells and antigen-presenting cells via CD40-CD40 ligand (CD40L). So far, transcriptional analyses of p40 have been carried out only using bacterial constituents such as LPS as stimuli. In the present study, we have characterized the transcriptional induction of p40 by CD40 ligation in a human B lymphoblastoid cell line, Daudi, and a human acute monocytic leukemia cell line, THP-1. These cells, stimulated by an agonistic monoclonal antibody against CD40 or by transfection with a CD40L expression vector, secreted p40 and showed enhanced p40 mRNA expression. Sequence analysis of the p40 promoter region identified two potential nuclear factor (NF)-kappaB binding sites conserved between mouse and human. Electrophoretic mobility shift assay revealed that the potential NF-kappaB binding sequence which is located around 120 bp upstream of the transcription initiation site in murine and human p40 genes formed an NF-kappaB complex with nuclear extract from Daudi cells stimulated by CD40 ligation. Moreover, transfection of Daudi cells with the polymerized NF-kappaB binding sequence ligated to a thymidine kinase/chloramphenicol acetyltransferase (CAT) reporter plasmid greatly induced CAT activity, but transfection with the polymerized mutated NF-kappaB binding sequence did not. These results suggest that the NF-kappaB binding site located around 120 bp upstream of the transcription initiation site in murine and human p40 promoter regions could be important for the p40 induction by CD40 ligation via activation of NF-kappaB. "
],
"offsets": [
[
0,
1863
]
]
}
] | [
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]
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},
{
"id": "9464836_T2",
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"text": [
"CD40"
],
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[
46,
50
]
],
"normalized": []
},
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"id": "9464836_T3",
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"CD40"
],
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365,
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]
],
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},
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"id": "9464836_T4",
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],
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"CD40"
],
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],
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}
] | [
{
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0,
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"transcript"
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32,
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"role": "Theme",
"ref_id": "9464836_T1"
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"id": "9464836_E3",
"type": "Binding",
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"ligation"
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51,
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{
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"-"
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"role": "Theme",
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"id": "9464836_E9",
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600,
608
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"role": "Theme",
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"id": "9464836_E10",
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"text": [
"secreted"
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834,
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"role": "Theme",
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}
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858,
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"role": "Theme",
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"role": "Theme",
"ref_id": "9464836_T18"
}
]
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"id": "9464836_E15",
"type": "Positive_regulation",
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"text": [
"important"
],
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1785,
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]
]
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"arguments": [
{
"role": "Theme",
"ref_id": "9464836_E16"
}
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"id": "9464836_E16",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
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1807,
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]
]
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"arguments": [
{
"role": "Theme",
"ref_id": "9464836_T20"
}
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"id": "9464836_E17",
"type": "Binding",
"trigger": {
"text": [
"ligation"
],
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[
1825,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9464836_T21"
}
]
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] | [
{
"id": "9464836_1",
"entity_ids": [
"9464836_T16",
"9464836_T17"
]
},
{
"id": "9464836_2",
"entity_ids": [
"9464836_T4",
"9464836_T5"
]
}
] | [] |
10359895 | 10359895 | [
{
"id": "10359895__text",
"type": "abstract",
"text": [
"Binding of YY1 and Oct1 to a novel element that downregulates expression of IL-5 in human T cells. \nBACKGROUND: IL-5 controls development of eosinophilia and has been shown to be involved in the pathogenesis of allergic diseases. In both atopic and nonatopic asthma, elevated IL-5 has been detected in peripheral blood and the airways. IL-5 is produced mainly by activated T cells, and its expression is regulated at the transcriptional level. OBJECTIVE: This study focuses on the functional analysis of the human IL-5 (hIL-5) promoter and characterization of cis -regulatory elements and transcription factors involved in the suppression of IL-5 transcription in T cells. METHODS: Methods used in this study include DNase I footprint assays, electrophoretic mobility shift assays, and functional analysis by mammalian cell transfection involving deletion analysis and site-directed mutagenesis. RESULTS: We identified 5 protein binding regions (BRs) located within the proximal hIL-5 promoter. Functional analysis indicates that the BRs are involved in control of hIL-5 promoter activity. Two of these regions, BR3 and BR4 located at positions -102 to -73, have not previously been described as regulators of IL-5 expression in T cells. We show that the BR3 sequence contains a novel negative regulatory element located at positions -90 to -79 of the hIL-5 promoter, which binds Oct1, octamer-like, and YY1 nuclear factors. Substitution mutations, which abolished binding of these proteins to the BR3 sequence, significantly increased hIL-5 promoter activity in activated T cells. CONCLUSION: We suggest that Oct1, YY1, and octamer-like factors binding to the -90/-79 sequence within the proximal IL-5 promoter are involved in suppression of IL-5 transcription in T cells. "
],
"offsets": [
[
0,
1774
]
]
}
] | [
{
"id": "10359895_T1",
"type": "Protein",
"text": [
"YY1"
],
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[
11,
14
]
],
"normalized": []
},
{
"id": "10359895_T2",
"type": "Protein",
"text": [
"Oct1"
],
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19,
23
]
],
"normalized": []
},
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"id": "10359895_T3",
"type": "Protein",
"text": [
"IL-5"
],
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76,
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]
],
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"id": "10359895_T4",
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"IL-5"
],
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]
],
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"id": "10359895_T5",
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],
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]
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],
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]
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],
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"hIL-5"
],
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]
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]
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"id": "10359895_T11",
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"hIL-5"
],
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"id": "10359895_T12",
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"id": "10359895_T13",
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"hIL-5"
],
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]
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"id": "10359895_T14",
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"Oct1"
],
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]
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"id": "10359895_T15",
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"YY1"
],
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1404,
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]
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"id": "10359895_T16",
"type": "Protein",
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"hIL-5"
],
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]
],
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"id": "10359895_T17",
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1610,
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]
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]
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"id": "10359895_T19",
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"IL-5"
],
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]
],
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},
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"id": "10359895_T20",
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"IL-5"
],
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]
],
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},
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"promoter"
],
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]
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},
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"id": "10359895_T35",
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]
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"id": "10359895_T40",
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]
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],
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1703,
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]
],
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}
] | [
{
"id": "10359895_E1",
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"Binding"
],
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0,
7
]
]
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0,
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]
]
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}
]
},
{
"id": "10359895_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"downregulates"
],
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48,
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]
]
},
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"role": "Theme",
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"expression"
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]
]
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}
]
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"id": "10359895_E5",
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"text": [
"elevated"
],
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267,
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]
]
},
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"role": "Theme",
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]
]
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}
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"id": "10359895_E7",
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"text": [
"regulated"
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404,
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]
]
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"role": "Theme",
"ref_id": "10359895_E6"
}
]
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"id": "10359895_E8",
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"text": [
"involved"
],
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611,
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]
]
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"role": "Theme",
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}
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},
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"id": "10359895_E9",
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"text": [
"suppression"
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627,
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]
]
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"role": "Theme",
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]
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"regulators"
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"expression"
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}
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"text": [
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"role": "Theme",
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"id": "10359895_E15",
"type": "Binding",
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"role": "Theme",
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}
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"type": "Binding",
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"binds"
],
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]
]
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"arguments": [
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"role": "Theme",
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}
]
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{
"id": "10359895_E17",
"type": "Negative_regulation",
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"text": [
"abolished"
],
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]
]
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"role": "Theme",
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}
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"id": "10359895_E18",
"type": "Negative_regulation",
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"text": [
"abolished"
],
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1455,
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]
]
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"arguments": [
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"role": "Theme",
"ref_id": "10359895_E19"
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"type": "Binding",
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"role": "Theme",
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"role": "Theme",
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}
]
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"id": "10359895_E21",
"type": "Positive_regulation",
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"text": [
"increased"
],
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]
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"role": "Theme",
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"type": "Binding",
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"binding"
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"binding"
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"role": "Theme",
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}
]
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"binding"
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"role": "Theme",
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"involved"
],
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]
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"role": "Theme",
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"role": "Cause",
"ref_id": "10359895_E23"
}
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]
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"suppression"
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"role": "Theme",
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"arguments": [
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"role": "Theme",
"ref_id": "10359895_T20"
}
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}
] | [
{
"id": "10359895_1",
"entity_ids": [
"10359895_T7",
"10359895_T8"
]
}
] | [] |
10037751 | 10037751 | [
{
"id": "10037751__text",
"type": "abstract",
"text": [
"T-cell expression of the human GATA-3 gene is regulated by a non-lineage-specific silencer. \nThe GATA-3 transcription factor is required for development of the T-cell lineage and Th2 cytokine gene expression in CD4 T-cells. We have mapped the DNase-I-hypersensitive (HS) regions of the human GATA-3 gene in T-cells and non-T-cells and studied their transcriptional activities. HS I-III, located 5' from the transcriptional initiation site, were found in hematopoietic and non-hematopoietic cells, whereas HS IV-VII, located 3' from the transcriptional start site, were exclusively observed in T-cells. Among these hypersensitive sites, two transcriptional control elements were found, one in the first intron of the GATA-3 gene and the other between 8.3 and 5.9 kilobases 5' from the GATA-3 transcriptional initiation site. The first intron acted as a strong transcriptional activator in a position-dependent manner and with no cell-type specificity. The upstream regulatory element could confer T-cell specificity to the GATA-3 promoter activity, and analysis of this region revealed a 707-base pair silencer that drastically inhibited GATA-3 promoter activity in non-T-cells. Two CAGGTG E-boxes, located at the 5'- and 3'-ends of the silencer, were necessary for this silencer activity. The 3'-CAGGTG E-box could bind USF proteins, the ubiquitous repressor ZEB, or the basic helix-loop-helix proteins E2A and HEB, and we showed that a competition between ZEB and E2A/HEB proteins is involved in the silencer activity. "
],
"offsets": [
[
0,
1520
]
]
}
] | [
{
"id": "10037751_T1",
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31,
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{
"id": "10037751_T2",
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"GATA-3"
],
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]
],
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},
{
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"type": "Protein",
"text": [
"CD4"
],
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211,
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]
],
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},
{
"id": "10037751_T4",
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"text": [
"GATA-3"
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292,
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],
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},
{
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{
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"id": "10037751_T7",
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"id": "10037751_T8",
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],
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},
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"id": "10037751_T9",
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"ZEB"
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]
],
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},
{
"id": "10037751_T10",
"type": "Protein",
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"E2A"
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]
],
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},
{
"id": "10037751_T11",
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"HEB"
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],
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},
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"id": "10037751_T12",
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"ZEB"
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]
],
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},
{
"id": "10037751_T13",
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"E2A"
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]
],
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"id": "10037751_T14",
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"HEB"
],
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],
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},
{
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"promoter"
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],
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},
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"text": [
"promoter"
],
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]
],
"normalized": []
}
] | [
{
"id": "10037751_E1",
"type": "Gene_expression",
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}
] | [] | [] |
7909357 | 7909357 | [
{
"id": "7909357__text",
"type": "abstract",
"text": [
"ERP, a new member of the ets transcription factor/oncoprotein family: cloning, characterization, and differential expression during B-lymphocyte development. \nThe ets gene family encodes a group of proteins which function as transcription factors under physiological conditions and, if aberrantly expressed, can cause cellular transformation. We have recently identified two regulatory elements in the murine immunoglobulin heavy-chain (IgH) enhancer, pi and microB, which exhibit striking similarity to binding sites for ets-related proteins. To identify ets-related transcriptional regulators expressed in pre-B lymphocytes that may interact with either the pi or the microB site, we have used a PCR approach with degenerate oligonucleotides encoding conserved sequences in all members of the ets family. We have cloned the gene for a new ets-related transcription factor, ERP (ets-related protein), from the murine pre-B cell line BASC 6C2 and from mouse lung tissue. The ERP protein contains a region of high homology with the ETS DNA-binding domain common to all members of the ets transcription factor/oncoprotein family. Three additional smaller regions show homology to the ELK-1 and SAP-1 genes, a subgroup of the ets gene family that interacts with the serum response factor. Full-length ERP expresses only negligible DNA-binding activity by itself. Removal of the carboxy terminus enables ERP to interact with a variety of ets-binding sites including the E74 site, the IgH enhancer pi site, and the lck promoter ets site, suggesting a carboxy-terminal negative regulatory domain. At least three ERP-related transcripts are expressed in a variety of tissues. However, within the B-cell lineage, ERP is highly expressed primarily at early stages of B-lymphocyte development, and expression declines drastically upon B-cell maturation, correlating with the enhancer activity of the IgH pi site. These data suggest that ERP might play a role in B-cell development and in IgH gene regulation. "
],
"offsets": [
[
0,
1999
]
]
}
] | [
{
"id": "7909357_T1",
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"ERP"
],
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[
0,
3
]
],
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"id": "7909357_T2",
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"ERP"
],
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875,
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]
],
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{
"id": "7909357_T3",
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],
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880,
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]
],
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},
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"id": "7909357_T19",
"type": "Entity",
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"promoter ets site"
],
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[
1514,
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]
],
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}
] | [
{
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] | [
{
"id": "7909357_1",
"entity_ids": [
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"7909357_T3"
]
}
] | [] |
8816395 | 8816395 | [
{
"id": "8816395__text",
"type": "abstract",
"text": [
"Requirements for induction of vitamin D-mediated gene regulation in normal human B lymphocytes. \nMature human lymphocytes are unique targets of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) in that vitamin D receptors (VDR) are not constitutively expressed, and specific cellular activation signals are required for both the up-regulation of VDR and establishment of reactivity to the lipophilic ligand. Treatment of B lymphocytes with the cytokine IL-4 (IL-4), in the absence of prior activation, induces a weak up-regulation of VDR expression but fails to generate vitamin D-responsive element (VDRE)-reactive nuclear protein complexes or to initiate the genomic transcription of 25-hydroxyvitamin D3 24-hydroxylase. Stimulation of B lymphocytes by either ligation of CD40 Ag or cross-linking the Ig receptor is also insufficient to render B lymphocytes responsive to 1 alpha,25(OH)2D3. However, this apparent lack of response to the secosterol can be overcome by stimulation of B lymphocytes with a combination of these cellular activation signals, which are sufficient to lead to G1 cell cycle progression. In the presence of 1 alpha,25(OH)2D3, cellular activation associated with stimulation of such a progression appears to be sufficient for the up-regulation of VDR message and protein and necessary for the establishment of VDRE binding complexes and the induction of 24-hydroxylase message. Furthermore, biologic functions are modulated, in that the hormone inhibits proliferation in a subset of the activated B cells. These observations suggest that reactivity to 1 alpha,25(OH)2D3 is tightly regulated in B lymphocytes, requiring specific signals for its initiation. "
],
"offsets": [
[
0,
1683
]
]
}
] | [
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"id": "8816395_T1",
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],
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222
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"id": "8816395_T2",
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]
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"id": "8816395_T4",
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],
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]
],
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},
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"id": "8816395_T5",
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},
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"id": "8816395_T6",
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"id": "8816395_T7",
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],
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"id": "8816395_T8",
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"id": "8816395_T9",
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"id": "8816395_T10",
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"text": [
"24-hydroxylase"
],
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[
1381,
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]
],
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}
] | [
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"id": "8816395_E1",
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252,
261
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"induces"
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"role": "Theme",
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"ligation"
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"In the presence of"
],
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"text": [
"In the presence of"
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"ref_id": "8816395_E14"
}
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"type": "Positive_regulation",
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"sufficient for the up-regulation"
],
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"necessary"
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"role": "Theme",
"ref_id": "8816395_E16"
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"id": "8816395_E16",
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"text": [
"induction"
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1368,
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8816395_T10"
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}
] | [
{
"id": "8816395_1",
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"8816395_T1",
"8816395_T2"
]
},
{
"id": "8816395_2",
"entity_ids": [
"8816395_T4",
"8816395_T5"
]
}
] | [] |
9247567 | 9247567 | [
{
"id": "9247567__text",
"type": "abstract",
"text": [
"Cyclosporin A interferes with the inducible degradation of NF-kappa B inhibitors, but not with the processing of p105/NF-kappa B1 in T cells. \nThe transcription factor NF-kappa B controls the induction of numerous cytokine promoters during the activation of T lymphocytes. Inhibition of T cell activation by the immunosuppressants cyclosporin A (CsA) and FK506 exerts a suppressive effect on the induction of these NF-kappa B-controlled cytokine promoters. We show for human Jurkat T leukemia cells, as well as human and mouse primary T lymphocytes, that this inhibitory effect is accompanied by an impaired nuclear translocation of the Rel proteins c-Rel, RelA/p65 and NF-kappa B1/p50, whereas the nuclear appearance of RelB remains unaffected. CsA does not interfere with the synthesis of Rel proteins, but prevents the inducible degradation of cytosolic NF-kappa B inhibitors I kappa B alpha and I kappa B beta upon T cell activation. CsA neither inhibits the processing of the NF-kappa B1 precursor p105 to p50, nor does it \"stabilize\" the C-terminal portion of p105, I kappa B gamma, which is degraded during p105 processing to mature p50. These results indicate that CsA interferes with a specific event in the signal-induced degradation of I kappa B alpha and I kappa B beta, but does not affect the processing of NF-kappa B1/p105 to p50. "
],
"offsets": [
[
0,
1346
]
]
}
] | [
{
"id": "9247567_T1",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
113,
117
]
],
"normalized": []
},
{
"id": "9247567_T2",
"type": "Protein",
"text": [
"NF-kappa B1"
],
"offsets": [
[
118,
129
]
],
"normalized": []
},
{
"id": "9247567_T3",
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681
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721,
725
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992
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] | [
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]
}
] | [] |
9130632 | 9130632 | [
{
"id": "9130632__text",
"type": "abstract",
"text": [
"Itk, a T cell-specific tyrosine kinase, is required for CD2-mediated interleukin-2 promoter activation in the human T cell line Jurkat. \nWe investigated the functional role of Itk, a member of the cytoplasmic tyrosine kinase Tec family, in T cell activation. Stimulation of either CD2 or T cell receptor (TCR)/CD3 on Tcells by monoclonal antibody-mediated cross-linking induced tyrosine phosphorylation of Itk, which was maximal as early as 1 min after stimulation. The tyrosine kinase activity in the anti-Itk immunoprecipitate was significantly activated upon these stimulations. Interleukin-2 (IL-2) promoter activity stimulated by cross-linking of CD2, TCR/CD3, and CD28 with antibodies was significantly reduced by transient expression of an Itk mutant lacking the kinase activity. The reduction paralleled a decrease in tyrosine phosphorylation of endogenous wild-type Itk. Stimulation of CD2 or TCR/CD3 induced activation of the nuclear factor of activated T cells (NFAT), the binding site of which is included in the IL-2 gene promoter. The activation of NFAT was also impaired by expression of the Itk mutant. These results demonstrate that Itk plays a role in IL-2 production, indicating a critical involvement of Itk in the initial stage of T cell activation by mediating signals from the TCR/CD3 complex, CD2, and CD28. "
],
"offsets": [
[
0,
1332
]
]
}
] | [
{
"id": "9130632_T1",
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"Itk"
],
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[
0,
3
]
],
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"CD2"
],
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[
56,
59
]
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"id": "9130632_T3",
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"interleukin-2"
],
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]
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"id": "9130632_T4",
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"Itk"
],
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[
176,
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]
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{
"id": "9130632_T5",
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"CD2"
],
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[
281,
284
]
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{
"id": "9130632_T6",
"type": "Protein",
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"Itk"
],
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[
406,
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]
],
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{
"id": "9130632_T7",
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"Itk"
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510
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"id": "9130632_T8",
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"id": "9130632_T9",
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"IL-2"
],
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597,
601
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"id": "9130632_T10",
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"CD2"
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655
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"id": "9130632_T11",
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"CD28"
],
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670,
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"id": "9130632_T12",
"type": "Protein",
"text": [
"Itk"
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[
747,
750
]
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},
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"id": "9130632_T13",
"type": "Protein",
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"Itk"
],
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[
875,
878
]
],
"normalized": []
},
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"id": "9130632_T14",
"type": "Protein",
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"CD2"
],
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[
895,
898
]
],
"normalized": []
},
{
"id": "9130632_T15",
"type": "Protein",
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"IL-2"
],
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[
1025,
1029
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],
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},
{
"id": "9130632_T16",
"type": "Protein",
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"Itk"
],
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[
1107,
1110
]
],
"normalized": []
},
{
"id": "9130632_T17",
"type": "Protein",
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"Itk"
],
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1153
]
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"id": "9130632_T18",
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],
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"id": "9130632_T19",
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"Itk"
],
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1224,
1227
]
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"id": "9130632_T20",
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"CD2"
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1320
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"id": "9130632_T21",
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1330
]
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"id": "9130632_T27",
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"tyrosine"
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378,
386
]
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},
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"id": "9130632_T30",
"type": "Entity",
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"promoter"
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603,
611
]
],
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"id": "9130632_T36",
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"tyrosine"
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834
]
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"id": "9130632_T40",
"type": "Entity",
"text": [
"promoter"
],
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[
1035,
1043
]
],
"normalized": []
}
] | [
{
"id": "9130632_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
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[
43,
51
]
]
},
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{
"role": "Theme",
"ref_id": "9130632_E2"
},
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"role": "Cause",
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}
]
},
{
"id": "9130632_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"activation"
],
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92,
102
]
]
},
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"ref_id": "9130632_T3"
},
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"id": "9130632_E3",
"type": "Positive_regulation",
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"Stimulation"
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270
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]
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"ref_id": "9130632_E4"
}
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"id": "9130632_E4",
"type": "Binding",
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"cross-linking"
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]
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},
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"id": "9130632_E5",
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"induced"
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377
]
]
},
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"role": "Theme",
"ref_id": "9130632_E7"
}
]
},
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"id": "9130632_E6",
"type": "Positive_regulation",
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"text": [
"induced"
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370,
377
]
]
},
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{
"role": "Theme",
"ref_id": "9130632_E7"
},
{
"role": "Cause",
"ref_id": "9130632_E3"
}
]
},
{
"id": "9130632_E7",
"type": "Phosphorylation",
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"text": [
"phosphorylation"
],
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402
]
]
},
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"role": "Theme",
"ref_id": "9130632_T6"
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"role": "Site",
"ref_id": "9130632_T27"
}
]
},
{
"id": "9130632_E8",
"type": "Positive_regulation",
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"text": [
"maximal"
],
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421,
428
]
]
},
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"role": "Theme",
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]
},
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"id": "9130632_E9",
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"text": [
"maximal"
],
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421,
428
]
]
},
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"role": "Theme",
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}
]
},
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"id": "9130632_E10",
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631
]
]
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"role": "Theme",
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"ref_id": "9130632_E13"
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"role": "Site",
"ref_id": "9130632_T30"
}
]
},
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"stimulated"
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621,
631
]
]
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{
"role": "Theme",
"ref_id": "9130632_T8"
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"role": "Site",
"ref_id": "9130632_T30"
}
]
},
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"id": "9130632_E12",
"type": "Positive_regulation",
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"text": [
"stimulated"
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621,
631
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]
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{
"role": "Theme",
"ref_id": "9130632_T8"
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},
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"role": "Site",
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}
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"cross-linking"
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{
"role": "Theme",
"ref_id": "9130632_T11"
}
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635,
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]
]
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"role": "Theme",
"ref_id": "9130632_T10"
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"reduced"
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"text": [
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"expression"
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}
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"decrease"
],
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]
]
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"role": "Theme",
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}
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"phosphorylation"
],
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]
]
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"role": "Theme",
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"included"
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"production"
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}
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]
}
] | [] |
8175775 | 8175775 | [
{
"id": "8175775__text",
"type": "abstract",
"text": [
"Functional block for 1 alpha,25-dihydroxyvitamin D3-mediated gene regulation in human B lymphocytes. \nElements necessary for the steroid hormone 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) to induce a biological response include the presence of specific intracellular receptors (vitamin D3 receptors (VDR)) and modulation of gene expression via hormone-activated receptor binding to regulatory regions of target genes. These parameters were examined in normal and Epstein-Barr virus-immortalized human B cells and compared with 1 alpha,25-(OH)2D3-responsive cells of the T and monocytic lineages. Although resting tonsillar B cells did not express VDR mRNA, activation of these cells with interleukin-4 induced VDR in the absence of exogenously supplemented 1 alpha,25-(OH)2D3. As indicators of hormone-mediated gene regulation we analyzed modulation of CD23, a common B cell/monocyte surface antigen, and 24-hydroxylase. 1 alpha,25-(OH)2D3 inhibited CD23 expression in U937 cells, yet failed to modulate CD23 expression in B cells. Furthermore, 1 alpha,25-(OH)2D3 induced 24-hydroxylase mRNA expression and metabolic activity in both U937 cells and lectin-activated T cells, yet failed to induce 24-hydroxylase mRNA or its metabolic activity in B cells. These findings suggest that although human B lymphocytes can express VDR mRNA and protein, they exhibit a functional block for vitamin D-dependent gene regulation. "
],
"offsets": [
[
0,
1427
]
]
}
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],
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287,
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]
],
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"id": "8175775_T2",
"type": "Protein",
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"VDR"
],
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[
309,
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]
],
"normalized": []
},
{
"id": "8175775_T3",
"type": "Protein",
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"VDR"
],
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656,
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]
],
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},
{
"id": "8175775_T4",
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],
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]
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],
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],
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"id": "8175775_T6",
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]
],
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],
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]
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"CD23"
],
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]
],
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],
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]
],
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],
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]
],
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},
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"id": "8175775_T12",
"type": "Protein",
"text": [
"VDR"
],
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1332,
1335
]
],
"normalized": []
}
] | [
{
"id": "8175775_E1",
"type": "Positive_regulation",
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],
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]
]
},
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]
]
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"role": "Theme",
"ref_id": "8175775_T3"
}
]
},
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"id": "8175775_E3",
"type": "Positive_regulation",
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"text": [
"induced"
],
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8175775_T5"
}
]
},
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"type": "Regulation",
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]
},
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"role": "Theme",
"ref_id": "8175775_T7"
}
]
},
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"type": "Negative_regulation",
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"text": [
"inhibited"
],
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]
]
},
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"role": "Theme",
"ref_id": "8175775_E7"
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"expression"
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]
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"type": "Regulation",
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"modulate"
],
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]
]
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"role": "Theme",
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]
},
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"role": "Theme",
"ref_id": "8175775_T9"
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"type": "Positive_regulation",
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"text": [
"induced"
],
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]
]
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"type": "Positive_regulation",
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"text": [
"induce"
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"role": "Theme",
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8175775_T12"
}
]
}
] | [
{
"id": "8175775_1",
"entity_ids": [
"8175775_T1",
"8175775_T2"
]
}
] | [] |
1531086 | 1531086 | [
{
"id": "1531086__text",
"type": "abstract",
"text": [
"A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site. \nA Rel-related, mitogen-inducible, kappa B-binding protein has been cloned as an immediate-early activation gene of human peripheral blood T cells. The cDNA has an open reading frame of 900 amino acids capable of encoding a 97-kDa protein. This protein is most similar to the 105-kDa precursor polypeptide of p50-NF-kappa B. Like the 105-kDa precursor, it contains an amino-terminal Rel-related domain of about 300 amino acids and a carboxy-terminal domain containing six full cell cycle or ankyrin repeats. In vitro-translated proteins, truncated downstream of the Rel domain and excluding the repeats, bind kappa B sites. We refer to the kappa B-binding, truncated protein as p50B by analogy with p50-NF-kappa B and to the full-length protein as p97. p50B is able to form heteromeric kappa B-binding complexes with RelB, as well as with p65 and p50, the two subunits of NF-kappa B. Transient-transfection experiments in embryonal carcinoma cells demonstrate a functional cooperation between p50B and RelB or p65 in transactivation of a reporter plasmid dependent on a kappa B site. The data imply the existence of a complex family of NF-kappa B-like transcription factors. "
],
"offsets": [
[
0,
1301
]
]
}
] | [
{
"id": "1531086_T1",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
50,
53
]
],
"normalized": []
},
{
"id": "1531086_T2",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
54,
58
]
],
"normalized": []
},
{
"id": "1531086_T3",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
435,
438
]
],
"normalized": []
},
{
"id": "1531086_T4",
"type": "Protein",
"text": [
"p50B"
],
"offsets": [
[
804,
808
]
],
"normalized": []
},
{
"id": "1531086_T5",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
825,
828
]
],
"normalized": []
},
{
"id": "1531086_T6",
"type": "Protein",
"text": [
"p97"
],
"offsets": [
[
874,
877
]
],
"normalized": []
},
{
"id": "1531086_T7",
"type": "Protein",
"text": [
"p50B"
],
"offsets": [
[
879,
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]
],
"normalized": []
},
{
"id": "1531086_T8",
"type": "Protein",
"text": [
"RelB"
],
"offsets": [
[
943,
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]
],
"normalized": []
},
{
"id": "1531086_T9",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
965,
968
]
],
"normalized": []
},
{
"id": "1531086_T10",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
973,
976
]
],
"normalized": []
},
{
"id": "1531086_T11",
"type": "Protein",
"text": [
"p50B"
],
"offsets": [
[
1119,
1123
]
],
"normalized": []
},
{
"id": "1531086_T12",
"type": "Protein",
"text": [
"RelB"
],
"offsets": [
[
1128,
1132
]
],
"normalized": []
},
{
"id": "1531086_T13",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1136,
1139
]
],
"normalized": []
}
] | [
{
"id": "1531086_E1",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
774,
781
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1531086_T4"
}
]
},
{
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"type": "Binding",
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"text": [
"binding"
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920,
927
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]
},
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"role": "Theme",
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}
]
},
{
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"type": "Binding",
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920,
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]
},
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"role": "Theme",
"ref_id": "1531086_T9"
}
]
},
{
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"type": "Binding",
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"binding"
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920,
927
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1531086_T7"
}
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},
{
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"type": "Binding",
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"text": [
"binding"
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920,
927
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]
},
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"role": "Theme",
"ref_id": "1531086_T8"
}
]
},
{
"id": "1531086_E6",
"type": "Binding",
"trigger": {
"text": [
"complexes"
],
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]
},
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{
"role": "Theme",
"ref_id": "1531086_T7"
},
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"role": "Theme",
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}
]
},
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"id": "1531086_E7",
"type": "Binding",
"trigger": {
"text": [
"complexes"
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928,
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},
"arguments": [
{
"role": "Theme",
"ref_id": "1531086_T7"
},
{
"role": "Theme",
"ref_id": "1531086_T8"
}
]
},
{
"id": "1531086_E8",
"type": "Binding",
"trigger": {
"text": [
"complexes"
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928,
937
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]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1531086_T7"
},
{
"role": "Theme",
"ref_id": "1531086_T9"
}
]
}
] | [] | [] |
7929355 | 7929355 | [
{
"id": "7929355__text",
"type": "abstract",
"text": [
"Protease inhibitors block lipopolysaccharide induction of tissue factor gene expression in human monocytic cells by preventing activation of c-Rel/p65 heterodimers. \nTissue factor (TF) is expressed rapidly by human monocytes exposed to bacterial endotoxin (lipopolysaccharide, or LPS). Transcriptional regulation is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site in the TF promoter. Nuclear translocation of cytosolic c-Rel/p65 heterodimers and other members of the NF-kappa B/Rel family requires dissociation and proteolytic degradation of the inhibitor protein, I kappa B alpha. The protease inhibitors N alpha-tosylphenylalanyl chloromethyl ketone (TPCK) and N alpha-tosyl-L-lysine chloromethyl ketone (TLCK) block activation of NF-kappa B/Rel proteins by preventing degradation of I kappa B alpha. To determine if TPCK and TLCK inhibited LPS induction of TF expression, freshly isolated human monocytes and monocytic THP-1 cells were pretreated with these inhibitors for 30 min before LPS stimulation. Both TPCK and TLCK inhibited LPS induction of TF protein, TF mRNA and TF promoter activity in a dose-dependent manner. These inhibitors specifically prevented degradation of I kappa B alpha and nuclear translocation of c-Rel/p65 heterodimers. In contrast, TPCK and TLCK did not block induction of an immediate-early gene encoding the transcription factor, Egr-1. Taken together, these data indicated that inhibiting nuclear translocation of c-Rel/p65 heterodimers prevented LPS induction of TF gene transcription in monocytic cells. "
],
"offsets": [
[
0,
1561
]
]
}
] | [
{
"id": "7929355_T1",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
141,
146
]
],
"normalized": []
},
{
"id": "7929355_T2",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
147,
150
]
],
"normalized": []
},
{
"id": "7929355_T3",
"type": "Protein",
"text": [
"Tissue factor"
],
"offsets": [
[
166,
179
]
],
"normalized": []
},
{
"id": "7929355_T4",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
181,
183
]
],
"normalized": []
},
{
"id": "7929355_T5",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
339,
344
]
],
"normalized": []
},
{
"id": "7929355_T6",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
345,
348
]
],
"normalized": []
},
{
"id": "7929355_T7",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
392,
394
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],
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},
{
"id": "7929355_T8",
"type": "Protein",
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"c-Rel"
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440,
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"id": "7929355_T9",
"type": "Protein",
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"p65"
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446,
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9115242 | 9115242 | [
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"id": "9115242__text",
"type": "abstract",
"text": [
"Transcriptional induction of collagenase-1 in differentiated monocyte-like (U937) cells is regulated by AP-1 and an upstream C/EBP-beta site. \nIn this report, we demonstrate that the AP-1 site and a distal promoter element regulate transcriptional induction of collagenase-1 during monocytic differentiation. Chloramphenicol acetyltransferase expression constructs containing regions of the human collagenase-1 promoter were stably or transiently transfected into U937 cells, and reporter activity was assessed at various times after the onset of phorbol 12-myristate 13-acetate (PMA)-mediated differentiation. Rapid and strong induction of promoter activity was lost in constructs with a mutant AP-1 element; however, at 16-96 h post-PMA, the mutant collagenase-1 promoter displayed AP-1 independent PMA-mediated transactivation. The AP-1 mutant constructs also showed delayed transcriptional activation in PMA-treated fibroblasts. Western and supershift analyses indicated that functional Jun and Fos proteins were present in nuclear extracts of PMA-differentiated U937 cells. Promoter deletion constructs demonstrated the potential role of distal promoter sequences in regulating collagenase-1 transcription. In particular, Western, supershift, and promoter deletion analyses suggested a role for CCAAT/enhancer-binding protein-beta (C/EBP-beta) binding site between -2010 and -1954 in regulating transcription of collagenase-1 in monocytic cells. Our findings suggest that distinct regulatory elements, acting somewhat independently of each other, control expression of collagenase-1. In addition, our data suggests that the rapid PMA-mediated induction of collagenase-1 transcription is controlled by a mechanism distinct from that regulating the sustained expression of this proteinase in activated macrophages. "
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}
] | [] |
9873041 | 9873041 | [
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"id": "9873041__text",
"type": "abstract",
"text": [
"Regulation of fas-ligand expression during activation-induced cell death in T lymphocytes via nuclear factor kappaB. \nT cell receptor engagement activates transcription factors important for cytokine gene regulation. Additionally, this signaling pathway also leads to activation-induced apoptosis in T lymphocytes that is dependent on FasL transcription and expression. Here we demonstrate that nuclear factor kappaB (NF-kappaB), which is involved in the transcriptional regulation of many cytokine genes expressed in activated lymphocytes, also plays a role in T cell activation-induced FasL expression. Inhibition of NF-kappaB activity in a T cell hybridoma leads to decreased FasL expression and apoptosis upon T cell receptor stimulation. We identified the NF-kappaB site in the FasL promoter that contributes to such regulation. Co-expression of p65 (Rel A) with the FasL promoter enhanced its activity, and co-expression of IkappaB dramatically inhibited the inducible promoter activity. In contrast, the transcription factor AP-1 is not required for activation-induced FasL promoter activity. These results define a role for NF-kappaB in mediating FasL expression during T cell activation. "
],
"offsets": [
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0,
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]
]
}
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14,
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]
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]
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{
"id": "9873041_1",
"entity_ids": [
"9873041_T6",
"9873041_T7"
]
}
] | [] |
9191057 | 9191057 | [
{
"id": "9191057__text",
"type": "abstract",
"text": [
"Relief of cyclin A gene transcriptional inhibition during activation of human primary T lymphocytes via CD2 and CD28 adhesion molecules. \nCyclin A transcription is cell cycle regulated and induced by cell proliferative signals. To understand the mechanisms underlined in this regulation in normal human cells, we have analysed in vivo protein-DNA interactions at the Cyclin A locus in primary T lymphocytes. Stimulation of purified T lymphocytes by a combination of monoclonal antibodies directed at CD2 and CD28 adhesion molecules gives rise to a long lasting proliferation in the absence of accessory cells. Cyclin A was observed after 4 days of costimulation with anti CD2 + CD28 whereas stimulation by anti CD2 or anti CD28 alone was not effective. In vivo genomic DMS footprinting revealed upstream of the major transcription initiation sites, the presence of at least three protein binding sites, two of which were constitutively occupied. They bind in vitro respectively ATF-1 and NF-Y proteins. The third site was occupied in quiescent cells or in cells stimulated by anti CD2 or anti CD28 alone. The mitogenic combination of anti CD2 + anti CD28 released the footprint as cells were committed to proliferation. Consistent with theses results, nuclear extracts prepared from quiescent cells formed a specific complex with this element, whereas extracts prepared from cells treated with anti CD2 + anti CD28 failed to do so after cells entered a proliferative state. "
],
"offsets": [
[
0,
1474
]
]
}
] | [
{
"id": "9191057_T1",
"type": "Protein",
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"cyclin A"
],
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[
10,
18
]
],
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},
{
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],
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104,
107
]
],
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},
{
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],
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112,
116
]
],
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},
{
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],
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138,
146
]
],
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},
{
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],
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367,
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]
],
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500,
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],
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}
] | [
{
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0,
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"role": "Theme",
"ref_id": "9191057_E3"
}
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"text": [
"induced"
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189,
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"ref_id": "9191057_E3"
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"trigger": {
"text": [
"interactions"
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347,
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"observed"
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"role": "Theme",
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"effective"
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"type": "Binding",
"trigger": {
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"bind"
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"role": "Theme",
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}
]
}
] | [] | [] |
8052854 | 8052854 | [
{
"id": "8052854__text",
"type": "abstract",
"text": [
"Inhibition of NF-kappa B by sodium salicylate and aspirin [see comments] \nThe transcription factor nuclear factor-kappa B (NF-kappa B) is critical for the inducible expression of multiple cellular and viral genes involved in inflammation and infection including interleukin-1 (IL-1), IL-6, and adhesion molecules. The anti-inflammatory drugs sodium salicylate and aspirin inhibited the activation of NF-kappa B, which further explains the mechanism of action of these drugs. This inhibition prevented the degradation of the NF-kappa B inhibitor, I kappa B, and therefore NF-kappa B was retained in the cytosol. Sodium salicylate and aspirin also inhibited NF-kappa B-dependent transcription from the Ig kappa enhancer and the human immunodeficiency virus (HIV) long terminal repeat (LTR) in transfected T cells. "
],
"offsets": [
[
0,
812
]
]
}
] | [
{
"id": "8052854_T1",
"type": "Protein",
"text": [
"IL-6"
],
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[
284,
288
]
],
"normalized": []
},
{
"id": "8052854_T2",
"type": "Protein",
"text": [
"Ig kappa"
],
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[
700,
708
]
],
"normalized": []
}
] | [
{
"id": "8052854_E1",
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"inhibited"
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"role": "Theme",
"ref_id": "8052854_E2"
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"id": "8052854_E2",
"type": "Positive_regulation",
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"text": [
"dependent"
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"role": "Theme",
"ref_id": "8052854_E3"
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"type": "Transcription",
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]
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"arguments": [
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"role": "Theme",
"ref_id": "8052854_T2"
}
]
}
] | [] | [] |
1537556 | 1537556 | [
{
"id": "1537556__text",
"type": "abstract",
"text": [
"Binding of erythroid and non-erythroid nuclear proteins to the silencer of the human epsilon-globin-encoding gene. \nTo clarify the molecular mechanisms involved in the developmental control of hemoglobin-encoding genes we have been studying the expression of these genes in human cells in continuous culture. We have previously reported the presence of a transcriptional control element with the properties of a silencer extending from -392 to -177 bp relative to the cap site of the human epsilon-globin-encoding gene [Cao et al., Proc.Natl.Acad.Sci.USA 86 (1989) 5306-5309]. We also showed that this silencer has stronger inhibitory activity in HeLa cells, as compared to K562 human erythroleukemia cells. Using deletion mutants and cis-cloned synthetic oligodeoxyribonucleotides in transient expression assays, nucleotide sequences responsible for this effect have now been further delimited to 44 bp located from -294 to -251 bp. Gel electrophoresis mobility shift assays and DNaseI footprinting assays demonstrate that these negative regulatory sequences are recognized differently by proteins present in nuclear extracts obtained from HeLa and K562 cells. Two binding proteins are detected in K562 nuclear extracts, while only one is found in extracts from HeLa cells. Possible mechanisms by which these proteins may regulate transcription of the epsilon-globin-encoding gene in erythroid and non-erythroid cells are discussed. "
],
"offsets": [
[
0,
1434
]
]
}
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{
"id": "1537556_T1",
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],
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85,
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{
"id": "1537556_T2",
"type": "Protein",
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"epsilon-globin"
],
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490,
504
]
],
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"id": "1537556_T3",
"type": "Protein",
"text": [
"DNaseI"
],
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980,
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],
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{
"id": "1537556_T4",
"type": "Protein",
"text": [
"epsilon-globin"
],
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1353,
1367
]
],
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}
] | [
{
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"text": [
"regulate"
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}
]
}
] | [] | [] |
10339475 | 10339475 | [
{
"id": "10339475__text",
"type": "abstract",
"text": [
"Monocyte arrest and transmigration on inflamed endothelium in shear flow is inhibited by adenovirus-mediated gene transfer of IkappaB-alpha. \nMobilization of nuclear factor-kappaB (NF-kappaB) activates transcription of genes encoding endothelial adhesion molecules and chemokines that contribute to monocyte infiltration critical in atherogenesis. Inhibition of NF-kappaB has been achieved by pharmacological and genetic approaches; however, monocyte interactions with activated endothelium in shear flow following gene transfer of the NF-kappaB inhibitor IkappaB-alpha have not been studied. We found that overexpression of IkappaB-alpha in endothelial cells using a recombinant adenovirus prevented tumor necrosis factor-alpha (TNF-alpha)-induced degradation of IkappaB-alpha and suppressed the upregulation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin mRNA and surface protein expression and the upregulation of transcripts for the chemokines monocyte chemoattractant protein 1 (MCP-1) and growth-related activity-alpha (GRO-alpha) by TNF-alpha. This was associated with a reduction in endothelial MCP-1 secretion and GRO-alpha immobilization. Adhesion assays under physiological shear flow conditions showed that firm arrest, spreading, and transmigration of monocytes on TNF-alpha-activated endothelium was markedly inhibited by IkappaB-alpha overexpression. Inhibition with monoclonal antibodies and peptide antagonists inferred that this was due to reduced expression of Ig integrin ligand as well as of chemokines specifically involved in these events. In contrast, rolling of monocytes was increased by IkappaB-alpha transfer and was partly mediated by P-selectin; however, it appeared to be unaffected by the inhibition of E-selectin induction. Thus, our data provide novel evidence that selective modulation of NF-kappaB by adenoviral transfer of IkappaB-alpha impairs the expression of multiple endothelial gene products required for subsequent monocyte arrest and emigration in shear flow and thus for monocyte infiltration in atherosclerotic plaques. "
],
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[
0,
2126
]
]
}
] | [
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"id": "10339475_T3",
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"id": "10339475_T4",
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],
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}
] | [
{
"id": "10339475_E1",
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]
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],
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]
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"role": "Theme",
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}
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},
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"id": "10339475_E7",
"type": "Positive_regulation",
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"text": [
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]
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"role": "Theme",
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},
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"id": "10339475_E8",
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]
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},
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"type": "Protein_catabolism",
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"role": "Theme",
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]
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},
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},
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},
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"role": "Theme",
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},
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},
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]
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"role": "Theme",
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}
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},
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]
},
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}
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},
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"text": [
"upregulation"
],
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797,
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]
]
},
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"role": "Theme",
"ref_id": "10339475_E28"
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]
},
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"type": "Positive_regulation",
"trigger": {
"text": [
"upregulation"
],
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]
},
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"role": "Theme",
"ref_id": "10339475_E26"
}
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},
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"id": "10339475_E25",
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"expression"
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"role": "Theme",
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}
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]
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"role": "Theme",
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}
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},
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"id": "10339475_E28",
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"trigger": {
"text": [
"expression"
],
"offsets": [
[
941,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T10"
}
]
},
{
"id": "10339475_E29",
"type": "Transcription",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
941,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T11"
}
]
},
{
"id": "10339475_E30",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
941,
951
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T10"
}
]
},
{
"id": "10339475_E31",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulation"
],
"offsets": [
[
960,
972
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_E34"
},
{
"role": "Cause",
"ref_id": "10339475_T16"
}
]
},
{
"id": "10339475_E32",
"type": "Positive_regulation",
"trigger": {
"text": [
"upregulation"
],
"offsets": [
[
960,
972
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_E33"
},
{
"role": "Cause",
"ref_id": "10339475_T16"
}
]
},
{
"id": "10339475_E33",
"type": "Transcription",
"trigger": {
"text": [
"transcripts"
],
"offsets": [
[
976,
987
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T15"
}
]
},
{
"id": "10339475_E34",
"type": "Transcription",
"trigger": {
"text": [
"transcripts"
],
"offsets": [
[
976,
987
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T13"
}
]
},
{
"id": "10339475_E35",
"type": "Negative_regulation",
"trigger": {
"text": [
"reduction"
],
"offsets": [
[
1137,
1146
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_E36"
}
]
},
{
"id": "10339475_E36",
"type": "Localization",
"trigger": {
"text": [
"secretion"
],
"offsets": [
[
1168,
1177
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T17"
}
]
},
{
"id": "10339475_E37",
"type": "Localization",
"trigger": {
"text": [
"immobilization"
],
"offsets": [
[
1192,
1206
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T18"
}
]
},
{
"id": "10339475_E38",
"type": "Gene_expression",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
1409,
1423
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T20"
}
]
},
{
"id": "10339475_E39",
"type": "Positive_regulation",
"trigger": {
"text": [
"overexpression"
],
"offsets": [
[
1409,
1423
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_E38"
}
]
},
{
"id": "10339475_E40",
"type": "Positive_regulation",
"trigger": {
"text": [
"transfer"
],
"offsets": [
[
1687,
1695
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_E41"
}
]
},
{
"id": "10339475_E41",
"type": "Gene_expression",
"trigger": {
"text": [
"transfer"
],
"offsets": [
[
1687,
1695
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T21"
}
]
},
{
"id": "10339475_E42",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibition"
],
"offsets": [
[
1780,
1790
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_E43"
}
]
},
{
"id": "10339475_E43",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
1805,
1814
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T23"
}
]
},
{
"id": "10339475_E44",
"type": "Gene_expression",
"trigger": {
"text": [
"transfer"
],
"offsets": [
[
1907,
1915
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_T24"
}
]
},
{
"id": "10339475_E45",
"type": "Positive_regulation",
"trigger": {
"text": [
"transfer"
],
"offsets": [
[
1907,
1915
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10339475_E44"
}
]
}
] | [
{
"id": "10339475_1",
"entity_ids": [
"10339475_T14",
"10339475_T15"
]
},
{
"id": "10339475_2",
"entity_ids": [
"10339475_T12",
"10339475_T13"
]
},
{
"id": "10339475_3",
"entity_ids": [
"10339475_T7",
"10339475_T8"
]
},
{
"id": "10339475_4",
"entity_ids": [
"10339475_T9",
"10339475_T10"
]
},
{
"id": "10339475_5",
"entity_ids": [
"10339475_T4",
"10339475_T5"
]
}
] | [] |
7518803 | 7518803 | [
{
"id": "7518803__text",
"type": "abstract",
"text": [
"Evidence for a trans-acting activator function regulating the expression of the human CD5 antigen. \nInterspecies somatic cell hybrids were generated by fusing the mouse T-lymphoma cell line, BW5147, with normal human T lymphocytes at different stages of differentiation. Thymocytes, activated peripheral T lymphocytes, or an activated T-cell clone were used as human partners, respectively, in three independent fusions. Irrespective of the human cell partner used for fusion, a certain number of hybrids lost CD5 surface expression over a period of time in culture. Analysis at the phenotype and genetic level showed that lack of CD5 expression was due neither to segregation of human autosome 11, on which the CD5 gene has been mapped, nor to deletion of the CD5 structural gene. Furthermore, loss of CD5 surface expression correlated with the absence of specific mRNA. Since these hybrids preferentially segregate human chromosomes, these results indicate the existence of a non-syntenic trans-active locus, or loci, positively controlling the expression of the human CD5 gene. "
],
"offsets": [
[
0,
1081
]
]
}
] | [
{
"id": "7518803_T1",
"type": "Protein",
"text": [
"CD5"
],
"offsets": [
[
86,
89
]
],
"normalized": []
},
{
"id": "7518803_T2",
"type": "Protein",
"text": [
"CD5"
],
"offsets": [
[
510,
513
]
],
"normalized": []
},
{
"id": "7518803_T3",
"type": "Protein",
"text": [
"CD5"
],
"offsets": [
[
631,
634
]
],
"normalized": []
},
{
"id": "7518803_T4",
"type": "Protein",
"text": [
"CD5"
],
"offsets": [
[
712,
715
]
],
"normalized": []
},
{
"id": "7518803_T5",
"type": "Protein",
"text": [
"CD5"
],
"offsets": [
[
761,
764
]
],
"normalized": []
},
{
"id": "7518803_T6",
"type": "Protein",
"text": [
"CD5"
],
"offsets": [
[
803,
806
]
],
"normalized": []
},
{
"id": "7518803_T7",
"type": "Protein",
"text": [
"CD5"
],
"offsets": [
[
1071,
1074
]
],
"normalized": []
}
] | [
{
"id": "7518803_E1",
"type": "Regulation",
"trigger": {
"text": [
"regulating"
],
"offsets": [
[
47,
57
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_E2"
}
]
},
{
"id": "7518803_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
62,
72
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_T1"
}
]
},
{
"id": "7518803_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"lost"
],
"offsets": [
[
505,
509
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_E4"
}
]
},
{
"id": "7518803_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
522,
532
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_T2"
}
]
},
{
"id": "7518803_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
635,
645
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_T3"
}
]
},
{
"id": "7518803_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"due"
],
"offsets": [
[
650,
653
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_E5"
}
]
},
{
"id": "7518803_E7",
"type": "Negative_regulation",
"trigger": {
"text": [
"loss"
],
"offsets": [
[
795,
799
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_E8"
}
]
},
{
"id": "7518803_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
815,
825
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_T6"
}
]
},
{
"id": "7518803_E9",
"type": "Transcription",
"trigger": {
"text": [
"absence"
],
"offsets": [
[
846,
853
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_T6"
}
]
},
{
"id": "7518803_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"positively controlling"
],
"offsets": [
[
1020,
1042
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_E11"
}
]
},
{
"id": "7518803_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1047,
1057
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7518803_T7"
}
]
}
] | [] | [] |
9710582 | 9710582 | [
{
"id": "9710582__text",
"type": "abstract",
"text": [
"The small GTP-binding protein Rho potentiates AP-1 transcription in T cells. \nThe Rho family of small GTP-binding proteins is involved in the regulation of cytoskeletal structure, gene transcription, specific cell fate development, and transformation. We demonstrate in this report that overexpression of an activated form of Rho enhances AP-1 activity in Jurkat T cells in the presence of phorbol myristate acetate (PMA), but activated Rho (V14Rho) has little or no effect on NFAT, Oct-1, and NF-kappaB enhancer element activities under similar conditions. Overexpression of a V14Rho construct incapable of membrane localization (CAAX deleted) abolishes PMA-induced AP-1 transcriptional activation. The effect of Rho on AP-1 is independent of the mitogen-activated protein kinase pathway, as a dominant-negative MEK and a MEK inhibitor (PD98059) did not affect Rho-induced AP-1 activity. V14Rho binds strongly to protein kinase Calpha (PKCalpha) in vivo; however, deletion of the CAAX site on V14Rho severely diminished this association. Evidence for a role for PKCalpha as an effector of Rho was obtained by the observation that coexpression of the N-terminal domain of PKCalpha blocked the effects of activated Rho plus PMA on AP-1 transcriptional activity. These data suggest that Rho potentiates AP-1 transcription during T-cell activation. "
],
"offsets": [
[
0,
1346
]
]
}
] | [
{
"id": "9710582_T1",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
483,
488
]
],
"normalized": []
},
{
"id": "9710582_T2",
"type": "Protein",
"text": [
"protein kinase Calpha"
],
"offsets": [
[
914,
935
]
],
"normalized": []
},
{
"id": "9710582_T3",
"type": "Protein",
"text": [
"PKCalpha"
],
"offsets": [
[
937,
945
]
],
"normalized": []
},
{
"id": "9710582_T4",
"type": "Protein",
"text": [
"PKCalpha"
],
"offsets": [
[
1063,
1071
]
],
"normalized": []
},
{
"id": "9710582_T5",
"type": "Protein",
"text": [
"PKCalpha"
],
"offsets": [
[
1172,
1180
]
],
"normalized": []
}
] | [
{
"id": "9710582_E1",
"type": "Regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
467,
473
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9710582_T1"
}
]
},
{
"id": "9710582_E2",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
896,
901
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9710582_T3"
}
]
},
{
"id": "9710582_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"diminished"
],
"offsets": [
[
1010,
1020
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9710582_E2"
}
]
},
{
"id": "9710582_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"coexpression"
],
"offsets": [
[
1131,
1143
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9710582_T5"
}
]
}
] | [
{
"id": "9710582_1",
"entity_ids": [
"9710582_T2",
"9710582_T3"
]
}
] | [] |
10438457 | 10438457 | [
{
"id": "10438457__text",
"type": "abstract",
"text": [
"Protein kinase C and calcineurin synergize to activate IkappaB kinase and NF-kappaB in T lymphocytes. \nThe nuclear factor of kappaB (NF-kappaB) is a ubiquitous transcription factor that is key in the regulation of the immune response and inflammation. T cell receptor (TCR) cross-linking is in part required for activation of NF-kappaB, which is dependent on the phosphorylation and degradation of IkappaBalpha. By using Jurkat and primary human T lymphocytes, we demonstrate that the simultaneous activation of two second messengers of the TCR-initiated signal transduction, protein kinase C (PKC) and calcineurin, results in the synergistic activation of the IkappaBalpha kinase (IKK) complex but not of another putative IkappaBalpha kinase, p90(rsk). We also demonstrate that the IKK complex, but not p90(rsk), is responsible for the in vivo phosphorylation of IkappaBalpha mediated by the co-activation of PKC and calcineurin. Each second messenger is necessary, as inhibition of either one reverses the activation of the IKK complex and IkappaBalpha phosphorylation in vivo. Overexpression of dominant negative forms of IKKalpha and -beta demonstrates that only IKKbeta is the target for PKC and calcineurin. These results indicate that within the TCR/CD3 signal transduction pathway both PKC and calcineurin are required for the effective activation of the IKK complex and NF-kappaB in T lymphocytes. "
],
"offsets": [
[
0,
1407
]
]
}
] | [
{
"id": "10438457_T1",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
398,
410
]
],
"normalized": []
},
{
"id": "10438457_T2",
"type": "Protein",
"text": [
"IkappaBalpha kinase"
],
"offsets": [
[
723,
742
]
],
"normalized": []
},
{
"id": "10438457_T3",
"type": "Protein",
"text": [
"p90(rsk)"
],
"offsets": [
[
744,
752
]
],
"normalized": []
},
{
"id": "10438457_T4",
"type": "Protein",
"text": [
"p90(rsk)"
],
"offsets": [
[
804,
812
]
],
"normalized": []
},
{
"id": "10438457_T5",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
864,
876
]
],
"normalized": []
},
{
"id": "10438457_T6",
"type": "Protein",
"text": [
"IkappaBalpha"
],
"offsets": [
[
1042,
1054
]
],
"normalized": []
},
{
"id": "10438457_T7",
"type": "Protein",
"text": [
"IKKalpha"
],
"offsets": [
[
1125,
1133
]
],
"normalized": []
},
{
"id": "10438457_T8",
"type": "Protein",
"text": [
"-beta"
],
"offsets": [
[
1138,
1143
]
],
"normalized": []
},
{
"id": "10438457_T9",
"type": "Protein",
"text": [
"IKKbeta"
],
"offsets": [
[
1167,
1174
]
],
"normalized": []
}
] | [
{
"id": "10438457_E1",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
363,
378
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_T1"
}
]
},
{
"id": "10438457_E2",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
383,
394
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_T1"
}
]
},
{
"id": "10438457_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"synergistic activation"
],
"offsets": [
[
631,
653
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_T3"
}
]
},
{
"id": "10438457_E4",
"type": "Regulation",
"trigger": {
"text": [
"responsible"
],
"offsets": [
[
817,
828
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_E6"
},
{
"role": "Cause",
"ref_id": "10438457_T4"
}
]
},
{
"id": "10438457_E5",
"type": "Regulation",
"trigger": {
"text": [
"responsible"
],
"offsets": [
[
817,
828
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_E6"
}
]
},
{
"id": "10438457_E6",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
845,
860
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_T5"
}
]
},
{
"id": "10438457_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"mediated"
],
"offsets": [
[
877,
885
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_E6"
}
]
},
{
"id": "10438457_E8",
"type": "Negative_regulation",
"trigger": {
"text": [
"reverses"
],
"offsets": [
[
995,
1003
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_E9"
}
]
},
{
"id": "10438457_E9",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1055,
1070
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_T6"
}
]
},
{
"id": "10438457_E10",
"type": "Regulation",
"trigger": {
"text": [
"target"
],
"offsets": [
[
1182,
1188
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "10438457_T9"
}
]
}
] | [] | [] |
9211847 | 9211847 | [
{
"id": "9211847__text",
"type": "abstract",
"text": [
"Inducible expression and phosphorylation of coactivator BOB.1/OBF.1 in T cells [see comments] \nBOB.1/OBF.1 is a transcriptional coactivator that is constitutively expressed in B cells and interacts with the Oct1 and Oct2 transcription factors. Upon activation of Jurkat T cells and primary murine thymocytes with phorbol esters and ionomycin, BOB.1/OBF.1 expression and transactivation function were induced. BOB.1/OBF.1 was phosphorylated at Ser184 both in vivo and in vitro, and this modification was required for inducible activation. Mutation of Ser184 also diminished transactivation function in B cells, suggesting that the activating phosphorylation that is inducible in T cells is constitutively present in B cells. Thus, BOB.1/OBF.1 is a transcriptional coactivator that is critically regulated by posttranslational modifications to mediate cell type-specific gene expression. "
],
"offsets": [
[
0,
886
]
]
}
] | [
{
"id": "9211847_T1",
"type": "Protein",
"text": [
"BOB.1"
],
"offsets": [
[
56,
61
]
],
"normalized": []
},
{
"id": "9211847_T2",
"type": "Protein",
"text": [
"OBF.1"
],
"offsets": [
[
62,
67
]
],
"normalized": []
},
{
"id": "9211847_T3",
"type": "Protein",
"text": [
"BOB.1"
],
"offsets": [
[
95,
100
]
],
"normalized": []
},
{
"id": "9211847_T4",
"type": "Protein",
"text": [
"OBF.1"
],
"offsets": [
[
101,
106
]
],
"normalized": []
},
{
"id": "9211847_T5",
"type": "Protein",
"text": [
"Oct1"
],
"offsets": [
[
207,
211
]
],
"normalized": []
},
{
"id": "9211847_T6",
"type": "Protein",
"text": [
"Oct2"
],
"offsets": [
[
216,
220
]
],
"normalized": []
},
{
"id": "9211847_T7",
"type": "Protein",
"text": [
"BOB.1"
],
"offsets": [
[
343,
348
]
],
"normalized": []
},
{
"id": "9211847_T8",
"type": "Protein",
"text": [
"OBF.1"
],
"offsets": [
[
349,
354
]
],
"normalized": []
},
{
"id": "9211847_T9",
"type": "Protein",
"text": [
"BOB.1"
],
"offsets": [
[
409,
414
]
],
"normalized": []
},
{
"id": "9211847_T10",
"type": "Protein",
"text": [
"OBF.1"
],
"offsets": [
[
415,
420
]
],
"normalized": []
},
{
"id": "9211847_T11",
"type": "Protein",
"text": [
"BOB.1"
],
"offsets": [
[
730,
735
]
],
"normalized": []
},
{
"id": "9211847_T12",
"type": "Protein",
"text": [
"OBF.1"
],
"offsets": [
[
736,
741
]
],
"normalized": []
},
{
"id": "9211847_T21",
"type": "Entity",
"text": [
"Ser184"
],
"offsets": [
[
443,
449
]
],
"normalized": []
}
] | [
{
"id": "9211847_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"Inducible"
],
"offsets": [
[
0,
9
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_E3"
}
]
},
{
"id": "9211847_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"Inducible"
],
"offsets": [
[
0,
9
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_E4"
}
]
},
{
"id": "9211847_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
10,
20
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T1"
}
]
},
{
"id": "9211847_E4",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
25,
40
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T1"
}
]
},
{
"id": "9211847_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expressed"
],
"offsets": [
[
163,
172
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T3"
}
]
},
{
"id": "9211847_E6",
"type": "Binding",
"trigger": {
"text": [
"interacts"
],
"offsets": [
[
188,
197
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T3"
},
{
"role": "Theme",
"ref_id": "9211847_T6"
}
]
},
{
"id": "9211847_E7",
"type": "Binding",
"trigger": {
"text": [
"interacts"
],
"offsets": [
[
188,
197
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T3"
},
{
"role": "Theme",
"ref_id": "9211847_T5"
}
]
},
{
"id": "9211847_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
355,
365
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T7"
}
]
},
{
"id": "9211847_E9",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
400,
407
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_E8"
}
]
},
{
"id": "9211847_E10",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylated"
],
"offsets": [
[
425,
439
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T9"
},
{
"role": "Site",
"ref_id": "9211847_T21"
}
]
},
{
"id": "9211847_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"required"
],
"offsets": [
[
503,
511
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T9"
},
{
"role": "Cause",
"ref_id": "9211847_E10"
}
]
},
{
"id": "9211847_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"activating"
],
"offsets": [
[
630,
640
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_E10"
}
]
},
{
"id": "9211847_E13",
"type": "Positive_regulation",
"trigger": {
"text": [
"inducible"
],
"offsets": [
[
665,
674
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_E12"
}
]
},
{
"id": "9211847_E14",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
794,
803
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9211847_T11"
}
]
}
] | [
{
"id": "9211847_1",
"entity_ids": [
"9211847_T1",
"9211847_T2"
]
},
{
"id": "9211847_2",
"entity_ids": [
"9211847_T11",
"9211847_T12"
]
},
{
"id": "9211847_3",
"entity_ids": [
"9211847_T9",
"9211847_T10"
]
},
{
"id": "9211847_4",
"entity_ids": [
"9211847_T3",
"9211847_T4"
]
},
{
"id": "9211847_5",
"entity_ids": [
"9211847_T7",
"9211847_T8"
]
}
] | [] |
8816450 | 8816450 | [
{
"id": "8816450__text",
"type": "abstract",
"text": [
"Analysis of the ligand-binding domain of human retinoic acid receptor alpha by site-directed mutagenesis. \nThree subtypes of retinoic acid receptors (RAR), termed RAR alpha, RAR beta, and RAR gamma, have been described. They are composed of different structural domains, including distinct domains for DNA and ligand binding. RARs specifically bind all-trans-retinoic acid (RA), 9-cis-RA, and retinoid analogs. In this study, we examined the functional role of cysteine and arginine residues in the ligand-binding domain of hRAR alpha (hRAR alpha-LBD, amino acids 154 to 462). All conserved cysteine and arginine residues in this domain were mutated by site-directed mutagenesis, and the mutant proteins were characterized by blocking reactions, ligand-binding experiments, transactivation assays, and protease mapping. Changes of any cysteine residue of the hRAR alpha-LBD had no significant influence on the binding of all-trans RA or 9-cis RA. Interestingly, residue C-235 is specifically important in antagonist binding. With respect to arginine residues, only the two single mutations of R-276 and R-394 to alanine showed a dramatic decrease of agonist and antagonist binding whereas the R272A mutation showed only a slight effect. For all other arginine mutations, no differences in affinity were detectable. The two mutations R217A and R294A caused an increased binding efficiency for antagonists but no change in agonist binding. From these results, we can conclude that electrostatic interactions of retinoids with the RAR alpha-LBD play a significant role in ligand binding. In addition, antagonists show distinctly different requirements for efficient binding, which may contribute to their interference in the ligand-inducible transactivation function of RAR alpha. "
],
"offsets": [
[
0,
1778
]
]
}
] | [
{
"id": "8816450_T1",
"type": "Protein",
"text": [
"human retinoic acid receptor alpha"
],
"offsets": [
[
41,
75
]
],
"normalized": []
},
{
"id": "8816450_T2",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
163,
172
]
],
"normalized": []
},
{
"id": "8816450_T3",
"type": "Protein",
"text": [
"RAR beta"
],
"offsets": [
[
174,
182
]
],
"normalized": []
},
{
"id": "8816450_T4",
"type": "Protein",
"text": [
"RAR gamma"
],
"offsets": [
[
188,
197
]
],
"normalized": []
},
{
"id": "8816450_T5",
"type": "Protein",
"text": [
"hRAR alpha"
],
"offsets": [
[
524,
534
]
],
"normalized": []
},
{
"id": "8816450_T6",
"type": "Protein",
"text": [
"hRAR alpha"
],
"offsets": [
[
536,
546
]
],
"normalized": []
},
{
"id": "8816450_T7",
"type": "Protein",
"text": [
"hRAR alpha"
],
"offsets": [
[
859,
869
]
],
"normalized": []
},
{
"id": "8816450_T8",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
1528,
1537
]
],
"normalized": []
},
{
"id": "8816450_T9",
"type": "Protein",
"text": [
"RAR alpha"
],
"offsets": [
[
1767,
1776
]
],
"normalized": []
}
] | [
{
"id": "8816450_E1",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
23,
30
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8816450_T1"
}
]
},
{
"id": "8816450_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"significant role"
],
"offsets": [
[
1549,
1565
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8816450_E3"
}
]
},
{
"id": "8816450_E3",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
1576,
1583
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8816450_T8"
}
]
},
{
"id": "8816450_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"interference"
],
"offsets": [
[
1702,
1714
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8816450_E5"
}
]
},
{
"id": "8816450_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"transactivation"
],
"offsets": [
[
1739,
1754
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8816450_T9"
}
]
}
] | [] | [] |
7645208 | 7645208 | [
{
"id": "7645208__text",
"type": "abstract",
"text": [
"Infection and replication of Tat- human immunodeficiency viruses: genetic analyses of LTR and tat mutations in primary and long-term human lymphoid cells. \nTat is an essential regulatory protein for the replication of human immunodeficiency virus (HIV). Mutations in the tat gene have been shown to block HIV replication in human T cells. Several studies have established that Tat releases an elongation block to the transcription of HIV long terminal repeat (LTR); however, it is not known whether this mechanism alone is sufficient to explain the block to HIV replication in human T cells when Tat is absent. It is possible that Tat is also needed for other functions during HIV replication. To test these hypotheses, we studied several tat mutants, including two stop codon mutants and one deletion mutant using replication-competent HIV-1 constructs carrying wild-type or mutant LTRs with modifications in the NF-kappa B and/or Sp1 binding sites. In this study, we show that Tat- HIV-1 with wild-type LTRs can replicate in HeLa cells, and the virus produced from HeLa cells can infect primary peripheral blood lymphocytes and macrophages. It was found that the propagation of the Tat mutants containing wild-type LTRs was less efficient than that of the LTR-modified Tat mutants. Large amounts of viral RNA and particles were synthesized in infections established using the tat mutants that contain modified LTRs. However, this efficient propagation of the LTR-modified tat mutants was restricted to some lymphoid cell lines that have been transformed with other viruses. Thus, despite its essential role for releasing an elongation block, Tat is not otherwise absolutely required for synthesis of full-length HIV transcripts and assembly of virus particles. Direct sequencing of the viral genomes and reinfection kinetics showed no evidence of wild-type reversion even after prolonged infection with the Tat- virus. The implications for in vivo HIV-1 replication and potential application of this system to the study of alternative Tat function are discussed. "
],
"offsets": [
[
0,
2065
]
]
}
] | [
{
"id": "7645208_T1",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
29,
32
]
],
"normalized": []
},
{
"id": "7645208_T2",
"type": "Protein",
"text": [
"tat"
],
"offsets": [
[
94,
97
]
],
"normalized": []
},
{
"id": "7645208_T3",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
156,
159
]
],
"normalized": []
},
{
"id": "7645208_T4",
"type": "Protein",
"text": [
"tat"
],
"offsets": [
[
271,
274
]
],
"normalized": []
},
{
"id": "7645208_T5",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
377,
380
]
],
"normalized": []
},
{
"id": "7645208_T6",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
596,
599
]
],
"normalized": []
},
{
"id": "7645208_T7",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
631,
634
]
],
"normalized": []
},
{
"id": "7645208_T8",
"type": "Protein",
"text": [
"tat"
],
"offsets": [
[
739,
742
]
],
"normalized": []
},
{
"id": "7645208_T9",
"type": "Protein",
"text": [
"Sp1"
],
"offsets": [
[
932,
935
]
],
"normalized": []
},
{
"id": "7645208_T10",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
979,
982
]
],
"normalized": []
},
{
"id": "7645208_T11",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1184,
1187
]
],
"normalized": []
},
{
"id": "7645208_T12",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1271,
1274
]
],
"normalized": []
},
{
"id": "7645208_T13",
"type": "Protein",
"text": [
"tat"
],
"offsets": [
[
1378,
1381
]
],
"normalized": []
},
{
"id": "7645208_T14",
"type": "Protein",
"text": [
"tat"
],
"offsets": [
[
1474,
1477
]
],
"normalized": []
},
{
"id": "7645208_T15",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1644,
1647
]
],
"normalized": []
},
{
"id": "7645208_T16",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
1909,
1912
]
],
"normalized": []
},
{
"id": "7645208_T17",
"type": "Protein",
"text": [
"Tat"
],
"offsets": [
[
2037,
2040
]
],
"normalized": []
}
] | [
{
"id": "7645208_E1",
"type": "Negative_regulation",
"trigger": {
"text": [
"absent"
],
"offsets": [
[
603,
609
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7645208_T6"
}
]
}
] | [] | [] |
8641346 | 8641346 | [
{
"id": "8641346__text",
"type": "abstract",
"text": [
"Interferon-gamma modulates the lipopolysaccharide-induced expression of AP-1 and NF-kappa B at the mRNA and protein level in human monocytes. \nInterferon-gamma (IFN-gamma) modulates the expression of several cytokines by human monocytes at the transcriptional level. In view of these findings, we analyzed the effects of IFN-gamma on the expression of different transcription factors in activated human monocytes. Priming of human monocytes with IFN-gamma resulted in the down regulation of c-fos and c-jun mRNA in response to stimulation with lipopolysaccharide (LPS) compared to the effects of LPS alone. Not only was this effect observed at the mRNA level, but activator protein-1 (AP-1) DNA binding capacity was affected as well, A strong reduction was observed in the LPS-induced DNA-binding activity of AP-1 in the presence of IFN-gamma. LPS-stimulated monocytes showed an increased expression of p105 mRNA, the precursor of the p50 subunit of the transcription factor nuclear factor-kappa B (NF-kappa B), while no effect was noticed on the expression of p65 mRNA. In contrast, IFN-gamma priming did not affect the expression of p105 transcripts but enhanced the expression of p65 mRNA (two-fold). Priming with IFN-gamma followed by LPS stimulation resulted in a further increase in the expression of p65 mRNA. This was due to an increase in the half-life of p65 mRNA (75 vs 150 minutes). Electrophoretic mobility shift assays (EMSAs) demonstrated that unstimulated monocytes predominantly expressed p50 NF-kappa B. Stimulation with LPS or IFN-gamma resulted in the expression of p50 and p65 subunits, while the combination of IFN-gamma plus LPS caused a further increase in the expression of NF-kappa B. With Western blotting, it was shown that nuclear extracts from monocytes contained p50 and p65 protein in response to LPS and IFN-gamma stimulation. However, the combined stimulation did not result in enhanced p50 and p65 protein expression. The effects of IFN-gamma on the transcription factors were specific, since no change was observed in the expression of NF-IL-6 or I kappa B alpha, the inhibitor of NF-kappa B. We conclude that the effects of IFN-gamma on the expression of the transcription factors AP-1 and NF-kappa B may be important for the modulatory effects of IFN-gamma on the cytokine expression in activated human monocytes. "
],
"offsets": [
[
0,
2352
]
]
}
] | [
{
"id": "8641346_T1",
"type": "Protein",
"text": [
"Interferon-gamma"
],
"offsets": [
[
0,
16
]
],
"normalized": []
},
{
"id": "8641346_T2",
"type": "Protein",
"text": [
"Interferon-gamma"
],
"offsets": [
[
143,
159
]
],
"normalized": []
},
{
"id": "8641346_T3",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
161,
170
]
],
"normalized": []
},
{
"id": "8641346_T4",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
321,
330
]
],
"normalized": []
},
{
"id": "8641346_T5",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
446,
455
]
],
"normalized": []
},
{
"id": "8641346_T6",
"type": "Protein",
"text": [
"c-fos"
],
"offsets": [
[
491,
496
]
],
"normalized": []
},
{
"id": "8641346_T7",
"type": "Protein",
"text": [
"c-jun"
],
"offsets": [
[
501,
506
]
],
"normalized": []
},
{
"id": "8641346_T8",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
833,
842
]
],
"normalized": []
},
{
"id": "8641346_T9",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
903,
907
]
],
"normalized": []
},
{
"id": "8641346_T10",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
935,
938
]
],
"normalized": []
},
{
"id": "8641346_T11",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1061,
1064
]
],
"normalized": []
},
{
"id": "8641346_T12",
"type": "Protein",
"text": [
"IFN-gamma"
],
"offsets": [
[
1084,
1093
]
],
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},
"arguments": [
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"ref_id": "8641346_T29"
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}
] | [
{
"id": "8641346_1",
"entity_ids": [
"8641346_T2",
"8641346_T3"
]
}
] | [] |
2269427 | 2269427 | [
{
"id": "2269427__text",
"type": "abstract",
"text": [
"An in vitro globin gene switching model based on differentiated embryonic stem cells. \nWe used mouse embryonic stem (ES) cells to study globin gene expression and switching in vitro. We show that ES-derived embryoid bodies express the full complement of mouse embryonic globin genes in the correct temporal order and that on further differentiation, a switch occurs to the fetal/adult genes. In addition, the erythroid-specific transcription factor NF-E1 was shown to be expressed coordinately with that of globin in embryoid bodies. We conclude from these experiments that the ES cell system provides a good model to study hematopoietic development. When the human epsilon- or beta-globin genes driven by the dominant control region (DCR) are introduced into this system, the human epsilon-globin gene, in contrast to the beta-globin gene, is not deregulated by the presence of the DCR and is expressed strictly as an embryonic gene. We conclude from this that the epsilon-globin gene is not regulated by competition with other genes in the human beta-globin locus. "
],
"offsets": [
[
0,
1067
]
]
}
] | [
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"id": "2269427_T1",
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],
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[
449,
454
]
],
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},
{
"id": "2269427_T2",
"type": "Protein",
"text": [
"epsilon-globin"
],
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[
783,
797
]
],
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},
{
"id": "2269427_T3",
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],
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823,
834
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],
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},
{
"id": "2269427_T4",
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],
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966,
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},
{
"id": "2269427_T5",
"type": "Protein",
"text": [
"beta-globin"
],
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[
1048,
1059
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}
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"ref_id": "2269427_T1"
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"ref_id": "2269427_T3"
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{
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"arguments": [
{
"role": "Theme",
"ref_id": "2269427_T4"
}
]
}
] | [] | [] |
7543076 | 7543076 | [
{
"id": "7543076__text",
"type": "abstract",
"text": [
"Lipopolysaccharide-induced E-selectin expression requires continuous presence of LPS and is inhibited by bactericidal/permeability-increasing protein. \nEndothelial cells stimulated by LPS express E-selectin, which plays an important role in mediating neutrophil adhesion during inflammation. E-selectin is induced within 1-2 h, peaks at 4-6 h, and gradually returns to basal level by 24 h. rBPI21, a recombinant N-terminal fragment of human bactericidal/permeability-increasing protein (BPI), inhibited LPS-induced E-selectin expression when added at the same time as, and up to 6 h after, LPS. Delayed administration of rBPI21 also affected LPS-mediated activation of the nuclear factor, NF-kappa B. Two to 4 h following LPS addition to endothelial cells, when NF-kappa B was already activated, addition of rBPI21 resulted in marked reduction of NF-kappa B detectable at 4 or 6 h. These results indicate that endothelial activation requires continuous presence of LPS, and rBPI21 acts to reverse LPS-mediated endothelial activation by interrupting the on-going LPS signal. "
],
"offsets": [
[
0,
1074
]
]
}
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37
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{
"id": "7543076_T2",
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196,
206
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{
"id": "7543076_T3",
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],
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292,
302
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{
"id": "7543076_T4",
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],
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441,
485
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{
"id": "7543076_T5",
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"BPI"
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487,
490
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{
"id": "7543076_T6",
"type": "Protein",
"text": [
"E-selectin"
],
"offsets": [
[
515,
525
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],
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}
] | [
{
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"type": "Positive_regulation",
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{
"role": "Theme",
"ref_id": "7543076_E1"
}
]
},
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"id": "7543076_E4",
"type": "Negative_regulation",
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"text": [
"inhibited"
],
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92,
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},
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"role": "Theme",
"ref_id": "7543076_E1"
}
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"id": "7543076_E5",
"type": "Gene_expression",
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"express"
],
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188,
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]
]
},
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"role": "Theme",
"ref_id": "7543076_T2"
}
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"id": "7543076_E6",
"type": "Positive_regulation",
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"induced"
],
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306,
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]
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},
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"role": "Theme",
"ref_id": "7543076_T3"
}
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"id": "7543076_E7",
"type": "Negative_regulation",
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"text": [
"inhibited"
],
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493,
502
]
]
},
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"role": "Theme",
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"induced"
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]
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] | [
{
"id": "7543076_1",
"entity_ids": [
"7543076_T4",
"7543076_T5"
]
}
] | [] |
1883525 | 1883525 | [
{
"id": "1883525__text",
"type": "abstract",
"text": [
"Regulation of M-CSF expression by M-CSF: role of protein kinase C and transcription factor NF kappa B. \nMacrophage-colony-stimulating factor (M-CSF), also referred to as CSF-1, regulates the survival, growth, differentiation and functional activity of monocytes by binding to a single class of high-affinity cell surface receptors, known to be the product of the c-fms protooncogene. The detection of both M-CSF and c-fms expression by cells of the monocyte lineage has suggested that M-CSF may act by an autocrine mechanism. Interestingly, it has been shown that M-CSF can induce the expression of its own gene. Although sensitivity to M-CSF can be modulated by regulation of receptor expression and function, M-CSF responsiveness is largely determined at a postreceptor level. To date, little is known about the intracellular pathway of M-CSF signal transduction. We have therefore investigated the changes in protein kinase C (PKC) activity upon exposure of monocytes to M-CSF. We show that M-CSF activates and translocates PKC. Inhibition of PKC by the isoquinoline derivative H7 abolishes induction of M-CSF by M-CSF. Furthermore, activation of PKC was pertussis-toxin-sensitive and was associated with the detection of an NF kappa B protein in nuclear extracts of M-CSF-induced blood monocytes but not in monocytes exposed to medium treatment only. The results suggest that M-CSF induction of M-CSF involves G proteins, PKC and NF kappa B. "
],
"offsets": [
[
0,
1446
]
]
}
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{
"id": "1883525_T1",
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],
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14,
19
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{
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"M-CSF"
],
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34,
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},
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"id": "1883525_T3",
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],
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104,
140
]
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},
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"id": "1883525_T4",
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"M-CSF"
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142,
147
]
],
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{
"id": "1883525_T5",
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"CSF-1"
],
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170,
175
]
],
"normalized": []
},
{
"id": "1883525_T6",
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"c-fms"
],
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363,
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]
],
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"id": "1883525_T7",
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406,
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]
],
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{
"id": "1883525_T8",
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],
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416,
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]
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],
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485,
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]
],
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],
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564,
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]
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]
],
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],
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711,
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]
],
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},
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],
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]
],
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},
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"M-CSF"
],
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]
],
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},
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"id": "1883525_T15",
"type": "Protein",
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"M-CSF"
],
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994,
999
]
],
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},
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"id": "1883525_T16",
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"M-CSF"
],
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1107,
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]
],
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},
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],
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1116,
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],
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},
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],
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]
],
"normalized": []
},
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"type": "Protein",
"text": [
"M-CSF"
],
"offsets": [
[
1399,
1404
]
],
"normalized": []
}
] | [
{
"id": "1883525_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_E2"
},
{
"role": "Cause",
"ref_id": "1883525_T2"
}
]
},
{
"id": "1883525_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
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20,
30
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_T1"
}
]
},
{
"id": "1883525_E3",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
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265,
272
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_T4"
}
]
},
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"id": "1883525_E4",
"type": "Gene_expression",
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"text": [
"expression"
],
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422,
432
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "1883525_T7"
}
]
},
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"id": "1883525_E5",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
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422,
432
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_T8"
}
]
},
{
"id": "1883525_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"act"
],
"offsets": [
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495,
498
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_T9"
}
]
},
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"id": "1883525_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"induce"
],
"offsets": [
[
574,
580
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_E8"
},
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"role": "Cause",
"ref_id": "1883525_T10"
}
]
},
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"id": "1883525_E8",
"type": "Gene_expression",
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"text": [
"expression"
],
"offsets": [
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585,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_T10"
}
]
},
{
"id": "1883525_E9",
"type": "Negative_regulation",
"trigger": {
"text": [
"abolishes"
],
"offsets": [
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1084,
1093
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_E10"
}
]
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"id": "1883525_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
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1094,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1883525_T16"
},
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"role": "Cause",
"ref_id": "1883525_T17"
}
]
},
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"id": "1883525_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"induction"
],
"offsets": [
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1386,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "1883525_T20"
},
{
"role": "Cause",
"ref_id": "1883525_T19"
}
]
}
] | [
{
"id": "1883525_1",
"entity_ids": [
"1883525_T3",
"1883525_T4"
]
}
] | [] |
9863501 | 9863501 | [
{
"id": "9863501__text",
"type": "abstract",
"text": [
"Phenylarsine oxide inhibits ex vivo HIV-1 expression. \nPhenylarsine oxide (PAO), which is described as an inhibitor of tyrosine phosphatase activity, inhibits H2O2 release from human peripheral blood mononuclear cells (PBMCs) as measured by electrochemistry. Since human immunodeficiency virus type 1 (HIV-1) replication is known to be favored under oxidative stress conditions, ex vivo experiments using uninfected PBMCs, primary monocytes or a latently infected promonocytic U1 cell line show that HIV-1 replication and reactivation, monitored by p24 antigen measurement, are inhibited by PAO in a time- and concentration-dependent manner. These observations can be linked with the inhibition of NF-kappa B activation when uninfected monocytes are induced by either tumor necrosis factor alpha (TNF-alpha) phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS). "
],
"offsets": [
[
0,
875
]
]
}
] | [
{
"id": "9863501_T1",
"type": "Protein",
"text": [
"p24 antigen"
],
"offsets": [
[
549,
560
]
],
"normalized": []
},
{
"id": "9863501_T2",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
768,
795
]
],
"normalized": []
},
{
"id": "9863501_T3",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
797,
806
]
],
"normalized": []
}
] | [] | [
{
"id": "9863501_1",
"entity_ids": [
"9863501_T2",
"9863501_T3"
]
}
] | [] |
9073544 | 9073544 | [
{
"id": "9073544__text",
"type": "abstract",
"text": [
"T-lymphocytes from individuals with filarial inflammatory disease have increased transendothelial migration in vitro. \nThe in vitro transendothelial migration of circulating filarial antigen-specific T-cells was examined in Wuchereria banerofti infection. Circulating T-cells from individuals with filaria-induced lymphatic pathology (LP) had significantly greater migration through unstimulated HUVEC monolayers than did T-cells from asymptomatic infected (MF) individuals (P = 0.04). In contrast to the MF individuals where no effect was seen, transendothelial migration of 48-hr filarial antigen stimulated T-cells from LP individuals was significantly (P = 0.01) greater than migration of 48-hr media-stimulated T-cells. In six of seven patients examined, inhibition of the VLA-4/VCAM-1 pathway resulted in greater than 50% inhibition of transendothelial migration of T-cells. "
],
"offsets": [
[
0,
881
]
]
}
] | [
{
"id": "9073544_T1",
"type": "Protein",
"text": [
"VLA-4"
],
"offsets": [
[
778,
783
]
],
"normalized": []
},
{
"id": "9073544_T2",
"type": "Protein",
"text": [
"VCAM-1"
],
"offsets": [
[
784,
790
]
],
"normalized": []
}
] | [] | [] | [] |
8196620 | 8196620 | [
{
"id": "8196620__text",
"type": "abstract",
"text": [
"Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site. \nExposure of monocytic cells to bacterial lipopolysaccharide (LPS) activates the NF-kappa B/Rel family of proteins and leads to the rapid induction of inflammatory gene products, including tissue factor (TF). TF is the primary cellular initiator of the coagulation protease cascades. Here we report the characterization of a nuclear complex from human monocytic cells that bound to a kappa B-like site, 5'-CGGAGTTTCC-3', in the 5'-flanking region of the human TF gene. This nuclear complex was activated by LPS with kinetics that preceded induction of the TF gene. In vitro binding studies demonstrated that the TF site bound translated c-Rel and p65 homodimers but not p50/p65 heterodimers or p50 homodimers. Base-pair substitutions in the TF site indicated that the presence of a cytosine at position 1 precluded binding of NF-kappa B. In fact, under low-ionic-strength conditions, the TF complex did not migrate with translated p50/p65 dimers but instead comigrated with c-Rel/p65 dimers. Antibodies against the NF-kappa B and Rel proteins and UV cross-linking studies revealed the presence of c-Rel and p65 and the absence of p50 in the TF complex and further showed that c-Rel/p65 heterodimers selectively bound to the TF kappa B-like site. Functional studies indicated that the TF site conferred LPS inducibility on a heterologous promoter and was transactivated by c-Rel or p65. Taken together, our results demonstrated that binding of c-Rel/p65 heterodimers to a novel kappa B-like site mediated LPS induction of TF gene expression in monocytic cells. "
],
"offsets": [
[
0,
1714
]
]
}
] | [
{
"id": "8196620_T1",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
107,
112
]
],
"normalized": []
},
{
"id": "8196620_T2",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
113,
116
]
],
"normalized": []
},
{
"id": "8196620_T3",
"type": "Protein",
"text": [
"tissue factor"
],
"offsets": [
[
343,
356
]
],
"normalized": []
},
{
"id": "8196620_T4",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
358,
360
]
],
"normalized": []
},
{
"id": "8196620_T5",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
363,
365
]
],
"normalized": []
},
{
"id": "8196620_T6",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
614,
616
]
],
"normalized": []
},
{
"id": "8196620_T7",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
710,
712
]
],
"normalized": []
},
{
"id": "8196620_T8",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
766,
768
]
],
"normalized": []
},
{
"id": "8196620_T9",
"type": "Protein",
"text": [
"c-Rel"
],
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[
791,
796
]
],
"normalized": []
},
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"id": "8196620_T10",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
801,
804
]
],
"normalized": []
},
{
"id": "8196620_T11",
"type": "Protein",
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"p50"
],
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824,
827
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],
"normalized": []
},
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"id": "8196620_T12",
"type": "Protein",
"text": [
"p65"
],
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828,
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],
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},
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"id": "8196620_T13",
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"p50"
],
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[
848,
851
]
],
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},
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"id": "8196620_T14",
"type": "Protein",
"text": [
"TF"
],
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[
895,
897
]
],
"normalized": []
},
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"id": "8196620_T15",
"type": "Protein",
"text": [
"TF"
],
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[
1042,
1044
]
],
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},
{
"id": "8196620_T16",
"type": "Protein",
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"p50"
],
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1085,
1088
]
],
"normalized": []
},
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"id": "8196620_T17",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1089,
1092
]
],
"normalized": []
},
{
"id": "8196620_T18",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1128,
1133
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],
"normalized": []
},
{
"id": "8196620_T19",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1134,
1137
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],
"normalized": []
},
{
"id": "8196620_T20",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1251,
1256
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],
"normalized": []
},
{
"id": "8196620_T21",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1261,
1264
]
],
"normalized": []
},
{
"id": "8196620_T22",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1284,
1287
]
],
"normalized": []
},
{
"id": "8196620_T23",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1295,
1297
]
],
"normalized": []
},
{
"id": "8196620_T24",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1330,
1335
]
],
"normalized": []
},
{
"id": "8196620_T25",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1336,
1339
]
],
"normalized": []
},
{
"id": "8196620_T26",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1378,
1380
]
],
"normalized": []
},
{
"id": "8196620_T27",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1438,
1440
]
],
"normalized": []
},
{
"id": "8196620_T28",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1526,
1531
]
],
"normalized": []
},
{
"id": "8196620_T29",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1535,
1538
]
],
"normalized": []
},
{
"id": "8196620_T30",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
1597,
1602
]
],
"normalized": []
},
{
"id": "8196620_T31",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1603,
1606
]
],
"normalized": []
},
{
"id": "8196620_T32",
"type": "Protein",
"text": [
"TF"
],
"offsets": [
[
1675,
1677
]
],
"normalized": []
},
{
"id": "8196620_T36",
"type": "Entity",
"text": [
"kappa B-like site"
],
"offsets": [
[
538,
555
]
],
"normalized": []
}
] | [
{
"id": "8196620_E1",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
96,
103
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8196620_T1"
}
]
},
{
"id": "8196620_E2",
"type": "Binding",
"trigger": {
"text": [
"binding"
],
"offsets": [
[
96,
103
]
]
},
"arguments": [
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] | [] |
9218534 | 9218534 | [
{
"id": "9218534__text",
"type": "abstract",
"text": [
"Role of the X2 box in activated transcription from the DRA promoter in B cells. \nWe investigated the function of the evolutionary conserved X2 box in the promoter of the HLA-DRA gene from the human major histocompatibility complex (MHC) in resting and activated B cells. NF-X2, which contains members of the AP-1/ATF/CREB families of transcription factors, interacts with the X2 box (5'-TGCGTCA-3') from positions -97 to -91 in the DRA promoter. In resting Raji cells, little to no binding to the X2 box was observed. In sharp contrast, in B cells treated with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), strong interactions between the X2 box and NF-X2 containing c-Fos were observed. As determined by transient expression and RNA analyses, the activation of protein kinase C (PKC) also increased rates of transcription from the wild-type DRA promoter but not from a DRA promoter bearing clustered point mutations in the X2 box. Since the co-expression with a dominant negative c-Fos abolished the responsiveness to TPA, we conclude that activated transcription of the DRA gene depends on interactions between the X2 box and NF-X2, which contains c-Fos. "
],
"offsets": [
[
0,
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]
}
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],
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}
] | [] | [] |
8613707 | 8613707 | [
{
"id": "8613707__text",
"type": "abstract",
"text": [
"Transcriptional basis for hyporesponsiveness of the human inducible nitric oxide synthase gene to lipopolysaccharide/interferon-gamma. \nThe work reported here resolves, at the level of gene regulation, the controversy as to whether or not human monocytes/macrophages can produce nitric oxide (NO) when stimulated with lipopolysaccharide (LPS), with or without co-stimulation by interferon-gamma (IFN-gamma). Studies included structural comparison of the promoters for human and mouse inducible NO synthase (iNOS) genes, transfection and assay of human and mouse iNOS promoter regions in response to LPS +/- IFN-gamma, and electrophoretic mobility shift assays of kappa B response elements. Two explanations for hyporesponsiveness of the human iNOS promoter to LPS +/- IFN-gamma were found: (1) multiple inactivating nucleotide substitutions in the human counterpart of the enhancer element that has been shown to regulate LPS/IFN-gamma induced expression of the mouse iNOS gene; and (2) and absence of one or more nuclear factors in human macrophages (e.g., an LPS-inducible nuclear factor-kappa B/Rel complex), that is (are) required for maximal expression of the gene. The importance of resolution of this controversy is that future research in this area should be directed toward the understanding of alternative mechanisms that can result in the successful production of NO. "
],
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[
0,
1379
]
]
}
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],
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]
],
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}
] | [
{
"id": "8613707_E1",
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]
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}
]
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"entity_ids": [
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"8613707_T6"
]
}
] | [] |
7516328 | 7516328 | [
{
"id": "7516328__text",
"type": "abstract",
"text": [
"Tolerance to lipopolysaccharide involves mobilization of nuclear factor kappa B with predominance of p50 homodimers. \nStimulation of the human monocytic cell line Mono Mac 6 with lipopolysaccharide (LPS) leads to rapid and transient expression of cytokines like tumor necrosis factor (TNF). When such cells are precultured for 2 days with a low dose of LPS (20 ng/ml) followed by stimulation with a high dose of LPS (1 microgram/ml), expression of the TNF gene is minimal, i.e. the cells are tolerant. In nuclear run-on analysis, such tolerant cells show only a low degree of transcription, indicating that tolerance operates at or upstream of the transcription level. The CD14 LPS receptor is, however, up-regulated (not down-regulated) in tolerant cells, and LPS can, in fact, still lead to activation of tolerant cells as evidenced by mobilization of the transcription factor nuclear factor kappa B (NF-kappa B). Resolution of the NF-kappa B complex in gel shift analysis shows that the binding protein, mobilized in naive Mono Mac 6 cells, consists mainly of p50-p65 heterodimers, while in tolerant cells, the p50 homodimer is predominant. This increase in p50 homodimers coincides with an increase in p105 mRNA, suggestive of a transcriptional up-regulation of p50. Reporter gene analysis reveals that the NF-kappa B complex mobilized in tolerant cells is functionally inactive in that NF-kappa B-dependent luciferase constructs containing the human immunodeficiency virus long terminal repeat or the TNF 5'-region show only minimal transactivation after LPS stimulation. Similar to Mono Mac 6 cells, primary blood monocytes, when precultured with a low dose of LPS, also become tolerant and produce little TNF after LPS stimulation. The tolerant blood monocytes also up-regulate CD14, and they mobilize NF-kappa B with a predominance of p50 homodimers. Taken together, these results demonstrate that tolerance to LPS is determined by post-receptor mechanisms that involve an altered composition of the NF-kappa B complex. "
],
"offsets": [
[
0,
2028
]
]
}
] | [
{
"id": "7516328_T1",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
101,
104
]
],
"normalized": []
},
{
"id": "7516328_T2",
"type": "Protein",
"text": [
"CD14"
],
"offsets": [
[
673,
677
]
],
"normalized": []
},
{
"id": "7516328_T3",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1063,
1066
]
],
"normalized": []
},
{
"id": "7516328_T4",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
1067,
1070
]
],
"normalized": []
},
{
"id": "7516328_T5",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1114,
1117
]
],
"normalized": []
},
{
"id": "7516328_T6",
"type": "Protein",
"text": [
"p50"
],
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[
1161,
1164
]
],
"normalized": []
},
{
"id": "7516328_T7",
"type": "Protein",
"text": [
"p105"
],
"offsets": [
[
1206,
1210
]
],
"normalized": []
},
{
"id": "7516328_T8",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1266,
1269
]
],
"normalized": []
},
{
"id": "7516328_T9",
"type": "Protein",
"text": [
"CD14"
],
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[
1785,
1789
]
],
"normalized": []
},
{
"id": "7516328_T10",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
1843,
1846
]
],
"normalized": []
},
{
"id": "7516328_T13",
"type": "Entity",
"text": [
"naive Mono Mac 6 cells"
],
"offsets": [
[
1020,
1042
]
],
"normalized": []
}
] | [
{
"id": "7516328_E1",
"type": "Localization",
"trigger": {
"text": [
"mobilization"
],
"offsets": [
[
41,
53
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7516328_T1"
}
]
},
{
"id": "7516328_E2",
"type": "Localization",
"trigger": {
"text": [
"mobilized"
],
"offsets": [
[
1007,
1016
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7516328_T3"
},
{
"role": "AtLoc",
"ref_id": "7516328_T13"
}
]
},
{
"id": "7516328_E3",
"type": "Localization",
"trigger": {
"text": [
"mobilized"
],
"offsets": [
[
1007,
1016
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7516328_T5"
}
]
},
{
"id": "7516328_E4",
"type": "Localization",
"trigger": {
"text": [
"mobilized"
],
"offsets": [
[
1007,
1016
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7516328_T4"
},
{
"role": "AtLoc",
"ref_id": "7516328_T13"
}
]
},
{
"id": "7516328_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1149,
1157
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7516328_T6"
}
]
},
{
"id": "7516328_E6",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
1194,
1202
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7516328_T7"
}
]
},
{
"id": "7516328_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"transcriptional up-regulation"
],
"offsets": [
[
1233,
1262
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7516328_T8"
}
]
},
{
"id": "7516328_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"up-regulate"
],
"offsets": [
[
1773,
1784
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7516328_T9"
}
]
}
] | [] | [] |
9442373 | 9442373 | [
{
"id": "9442373__text",
"type": "abstract",
"text": [
"Regulation of NF-kappa B activity by I kappa B alpha and I kappa B beta stability. \nTranscription factor NF-kappa B must be released from cytoplasmic inhibitory molecules (I kappa Bs) in order to move to the nucleus and to activate its target genes. Little is known about the mechanisms regulating the maintenance of constitutive nuclear NF-kappa B in some cell-types and of sustained nuclear NF-kappa B activity after stimulation. Increased turnover has been implicated in the regulation of constitutive NF-kappa B activity in mature B cells. We therefore compared the turnover of I kappa B alpha and I kappa B beta in mature B cells and HeLa cells. Both proteins display a high turnover in B cells although I kappa B beta is considerably more stable than I kappa B alpha. The half-life of both inhibitors is increased in HeLa cells. In contrast, all other NF-kappa B/I kappa B molecules tested are relatively stable in both cell-types. The elevated turnover of endogenous I kappa B alpha in Namalwa cells is inhibited by a proteasome inhibitor and thus seems to be driven by the same degradation machinery as the slower turnover in non-B cells. Furthermore, we investigated the processes involved in persistent activation of NF-kappa B. TNF-alpha signaling leads to a rapid depletion of cellular I kappa B beta pools. I kappa B alpha is efficiently resynthesized whereas I kappa B beta levels stay low for a prolonged time. NF-kappa B binding activity can be detected for several hours after stimulation. We found that removal of the TNF-alpha containing medium causes a rapid decrease in nuclear NF-kappa B. A phosphoform of newly synthesized I kappa B alpha is visible when degradation by the proteasome is inhibited and new I kappa B alpha displays the same properties regarding phosphorylation and degradation in response to a second inducer. There is no significant difference in the turnover of pre- and post-inductive I kappa B alpha. These observations suggest that resynthesis of I kappa B alpha and removal of the stimulus are obligatory steps for the inactivation of nuclear NF kappa B. "
],
"offsets": [
[
0,
2100
]
]
}
] | [
{
"id": "9442373_T1",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
37,
52
]
],
"normalized": []
},
{
"id": "9442373_T2",
"type": "Protein",
"text": [
"I kappa B beta"
],
"offsets": [
[
57,
71
]
],
"normalized": []
},
{
"id": "9442373_T3",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
582,
597
]
],
"normalized": []
},
{
"id": "9442373_T4",
"type": "Protein",
"text": [
"I kappa B beta"
],
"offsets": [
[
602,
616
]
],
"normalized": []
},
{
"id": "9442373_T5",
"type": "Protein",
"text": [
"I kappa B beta"
],
"offsets": [
[
709,
723
]
],
"normalized": []
},
{
"id": "9442373_T6",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
757,
772
]
],
"normalized": []
},
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"id": "9442373_T7",
"type": "Protein",
"text": [
"I kappa B alpha"
],
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[
974,
989
]
],
"normalized": []
},
{
"id": "9442373_T8",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1239,
1248
]
],
"normalized": []
},
{
"id": "9442373_T9",
"type": "Protein",
"text": [
"I kappa B beta"
],
"offsets": [
[
1298,
1312
]
],
"normalized": []
},
{
"id": "9442373_T10",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1320,
1335
]
],
"normalized": []
},
{
"id": "9442373_T11",
"type": "Protein",
"text": [
"I kappa B beta"
],
"offsets": [
[
1373,
1387
]
],
"normalized": []
},
{
"id": "9442373_T12",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
1536,
1545
]
],
"normalized": []
},
{
"id": "9442373_T13",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1646,
1661
]
],
"normalized": []
},
{
"id": "9442373_T14",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1729,
1744
]
],
"normalized": []
},
{
"id": "9442373_T15",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1927,
1942
]
],
"normalized": []
},
{
"id": "9442373_T16",
"type": "Protein",
"text": [
"I kappa B alpha"
],
"offsets": [
[
1991,
2006
]
],
"normalized": []
}
] | [
{
"id": "9442373_E1",
"type": "Protein_catabolism",
"trigger": {
"text": [
"stability"
],
"offsets": [
[
72,
81
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T2"
}
]
},
{
"id": "9442373_E2",
"type": "Protein_catabolism",
"trigger": {
"text": [
"stability"
],
"offsets": [
[
72,
81
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T1"
}
]
},
{
"id": "9442373_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
810,
819
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T5"
}
]
},
{
"id": "9442373_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"increased"
],
"offsets": [
[
810,
819
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T6"
}
]
},
{
"id": "9442373_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"leads"
],
"offsets": [
[
1259,
1264
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_E6"
}
]
},
{
"id": "9442373_E6",
"type": "Negative_regulation",
"trigger": {
"text": [
"depletion"
],
"offsets": [
[
1276,
1285
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T9"
}
]
},
{
"id": "9442373_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"resynthesized"
],
"offsets": [
[
1351,
1364
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T10"
}
]
},
{
"id": "9442373_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"levels stay low"
],
"offsets": [
[
1388,
1403
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T11"
}
]
},
{
"id": "9442373_E9",
"type": "Negative_regulation",
"trigger": {
"text": [
"removal"
],
"offsets": [
[
1521,
1528
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T12"
}
]
},
{
"id": "9442373_E10",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphoform"
],
"offsets": [
[
1613,
1624
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T13"
}
]
},
{
"id": "9442373_E11",
"type": "Gene_expression",
"trigger": {
"text": [
"synthesized"
],
"offsets": [
[
1634,
1645
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T13"
}
]
},
{
"id": "9442373_E12",
"type": "Positive_regulation",
"trigger": {
"text": [
"when"
],
"offsets": [
[
1673,
1677
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_E10"
},
{
"role": "Cause",
"ref_id": "9442373_E15"
}
]
},
{
"id": "9442373_E13",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
1678,
1689
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T13"
}
]
},
{
"id": "9442373_E14",
"type": "Positive_regulation",
"trigger": {
"text": [
"by"
],
"offsets": [
[
1690,
1692
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_E13"
}
]
},
{
"id": "9442373_E15",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibited"
],
"offsets": [
[
1711,
1720
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_E13"
}
]
},
{
"id": "9442373_E16",
"type": "Phosphorylation",
"trigger": {
"text": [
"phosphorylation"
],
"offsets": [
[
1784,
1799
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T14"
}
]
},
{
"id": "9442373_E17",
"type": "Protein_catabolism",
"trigger": {
"text": [
"degradation"
],
"offsets": [
[
1804,
1815
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T14"
}
]
},
{
"id": "9442373_E18",
"type": "Positive_regulation",
"trigger": {
"text": [
"in response to"
],
"offsets": [
[
1816,
1830
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_E17"
}
]
},
{
"id": "9442373_E19",
"type": "Positive_regulation",
"trigger": {
"text": [
"in response to"
],
"offsets": [
[
1816,
1830
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_E16"
}
]
},
{
"id": "9442373_E20",
"type": "Gene_expression",
"trigger": {
"text": [
"resynthesis"
],
"offsets": [
[
1976,
1987
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9442373_T16"
}
]
}
] | [] | [] |
9115394 | 9115394 | [
{
"id": "9115394__text",
"type": "abstract",
"text": [
"A negative role for phosphoinositide 3-kinase in T-cell antigen receptor function. \nBACKGROUND: A delicate balance between positive and negative regulatory mechanisms during T-cell activation determines the specificity and magnitude of an immune response. Phosphoinositide 3-kinase (PI 3-kinase) is activated by a diverse set of receptors that determine T-cell function, including the T-cell antigen receptor (TCR), the costimulatory receptor CD28, and negative regulators of T-cell activation such as CTLA-4. PI 3-kinase is also regulated by the haematopoietic cytokines that determine T-cell differentiation and lymphocyte proliferation. PI 3-kinase can thus dynamically influence the outcome of the immune reactions at various stages. In this study, we investigated the importance of PI 3-kinase in TCR-directed T-cell activation using activated or inhibitory versions of PI 3-kinase. RESULTS: Certain aspects of TCR responses such as the induction of transcriptional activity of AP1 and serum response factor were not affected by expression of the mutant forms of PI 3-kinase. We found, however, that PI 3-kinase profoundly influenced the transactivation capacity of 'nuclear factor of activated T cells' (NF-AT) elicited by the TCR: expression of an activated form of PI 3-kinase inhibited TCR-mediated NF-AT responses, whereas expression of a dominant negative mutant of PI 3-kinase potently enhanced TCR-controlled NF-AT induction. These effects of PI 3-kinase were not mediated by previously identified PI 3-kinase effectors, such as protein kinase B, a positive regulator of PI 3-kinase, or the GTPase Rac, and are therefore likely to involve a novel, as yet unknown, effector molecule. CONCLUSIONS: Our results establish that PI 3-kinase can both positively and negatively regulate T-cell function, and uncover a previously unrecognized function for PI 3-kinase in T cells as a selective negative regulator of TCR-signalling events and therefore as a determinant of T-cell homeostasis. "
],
"offsets": [
[
0,
1996
]
]
}
] | [
{
"id": "9115394_T1",
"type": "Protein",
"text": [
"phosphoinositide 3-kinase"
],
"offsets": [
[
20,
45
]
],
"normalized": []
},
{
"id": "9115394_T2",
"type": "Protein",
"text": [
"Phosphoinositide 3-kinase"
],
"offsets": [
[
256,
281
]
],
"normalized": []
},
{
"id": "9115394_T3",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
283,
294
]
],
"normalized": []
},
{
"id": "9115394_T4",
"type": "Protein",
"text": [
"CD28"
],
"offsets": [
[
443,
447
]
],
"normalized": []
},
{
"id": "9115394_T5",
"type": "Protein",
"text": [
"CTLA-4"
],
"offsets": [
[
502,
508
]
],
"normalized": []
},
{
"id": "9115394_T6",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
510,
521
]
],
"normalized": []
},
{
"id": "9115394_T7",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
640,
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]
],
"normalized": []
},
{
"id": "9115394_T8",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
787,
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]
],
"normalized": []
},
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"id": "9115394_T9",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
875,
886
]
],
"normalized": []
},
{
"id": "9115394_T10",
"type": "Protein",
"text": [
"PI 3-kinase"
],
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[
1068,
1079
]
],
"normalized": []
},
{
"id": "9115394_T11",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
1105,
1116
]
],
"normalized": []
},
{
"id": "9115394_T12",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
1273,
1284
]
],
"normalized": []
},
{
"id": "9115394_T13",
"type": "Protein",
"text": [
"PI 3-kinase"
],
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1377,
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]
],
"normalized": []
},
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"id": "9115394_T14",
"type": "Protein",
"text": [
"PI 3-kinase"
],
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1456,
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]
],
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},
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"id": "9115394_T15",
"type": "Protein",
"text": [
"PI 3-kinase"
],
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1511,
1522
]
],
"normalized": []
},
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"id": "9115394_T16",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
1584,
1595
]
],
"normalized": []
},
{
"id": "9115394_T17",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
1736,
1747
]
],
"normalized": []
},
{
"id": "9115394_T18",
"type": "Protein",
"text": [
"PI 3-kinase"
],
"offsets": [
[
1860,
1871
]
],
"normalized": []
}
] | [
{
"id": "9115394_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
299,
308
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9115394_T3"
},
{
"role": "Cause",
"ref_id": "9115394_T4"
}
]
},
{
"id": "9115394_E2",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
299,
308
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9115394_T3"
}
]
},
{
"id": "9115394_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"activated"
],
"offsets": [
[
299,
308
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9115394_T3"
},
{
"role": "Cause",
"ref_id": "9115394_T5"
}
]
},
{
"id": "9115394_E4",
"type": "Negative_regulation",
"trigger": {
"text": [
"negative regulators"
],
"offsets": [
[
453,
472
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9115394_E3"
},
{
"role": "Cause",
"ref_id": "9115394_T5"
}
]
},
{
"id": "9115394_E5",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
530,
539
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9115394_T6"
}
]
},
{
"id": "9115394_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1034,
1044
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9115394_T10"
}
]
},
{
"id": "9115394_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
1238,
1248
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9115394_T12"
}
]
},
{
"id": "9115394_E8",
"type": "Positive_regulation",
"trigger": {
"text": [
"positive regulator"
],
"offsets": [
[
1562,
1580
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9115394_T16"
}
]
}
] | [
{
"id": "9115394_1",
"entity_ids": [
"9115394_T2",
"9115394_T3"
]
}
] | [] |
9111040 | 9111040 | [
{
"id": "9111040__text",
"type": "abstract",
"text": [
"Oncogenic forms of NOTCH1 lacking either the primary binding site for RBP-Jkappa or nuclear localization sequences retain the ability to associate with RBP-Jkappa and activate transcription. \nTruncated forms of the NOTCH1 transmembrane receptor engineered to resemble mutant forms of NOTCH1 found in certain cases of human T cell leukemia/lymphoma (T-ALL) efficiently induce T-ALL when expressed in the bone marrow of mice. Unlike full-sized NOTCH1, two such truncated forms of the protein either lacking a major portion of the extracellular domain (DeltaE) or consisting only of the intracellular domain (ICN) were found to activate transcription in cultured cells, presumably through RBP-Jkappa response elements within DNA. Both truncated forms also bound to the transcription factor RBP-Jkappa in extracts prepared from human and murine T-ALL cell lines. Transcriptional activation required the presence of a weak RBP-Jkappa-binding site within the NOTCH1 ankyrin repeat region of the intracellular domain. Unexpectedly, a second, stronger RBP-Jkappa-binding site, which lies within the intracellular domain close to the transmembrane region and significantly augments association with RBP-Jkappa, was not needed for oncogenesis or for transcriptional activation. While ICN appeared primarily in the nucleus, DeltaE localized to cytoplasmic and nuclear membranes, suggesting that intranuclear localization is not essential for oncogenesis or transcriptional activation. In support of this interpretation, mutation of putative nuclear localization sequences decreased nuclear localization and increased transcriptional activation by membrane-bound DeltaE. Transcriptional activation by this mutant form of membrane-bound DeltaE was approximately equivalent to that produced by intranuclear ICN. These data are most consistent with NOTCH1 oncogenesis and transcriptional activation being independent of association with RBP-Jkappa at promoter sites. "
],
"offsets": [
[
0,
1952
]
]
}
] | [
{
"id": "9111040_T1",
"type": "Protein",
"text": [
"NOTCH1"
],
"offsets": [
[
19,
25
]
],
"normalized": []
},
{
"id": "9111040_T2",
"type": "Protein",
"text": [
"RBP-Jkappa"
],
"offsets": [
[
70,
80
]
],
"normalized": []
},
{
"id": "9111040_T3",
"type": "Protein",
"text": [
"RBP-Jkappa"
],
"offsets": [
[
152,
162
]
],
"normalized": []
},
{
"id": "9111040_T4",
"type": "Protein",
"text": [
"NOTCH1"
],
"offsets": [
[
215,
221
]
],
"normalized": []
},
{
"id": "9111040_T5",
"type": "Protein",
"text": [
"NOTCH1"
],
"offsets": [
[
284,
290
]
],
"normalized": []
},
{
"id": "9111040_T6",
"type": "Protein",
"text": [
"NOTCH1"
],
"offsets": [
[
442,
448
]
],
"normalized": []
},
{
"id": "9111040_T7",
"type": "Protein",
"text": [
"RBP-Jkappa"
],
"offsets": [
[
686,
696
]
],
"normalized": []
},
{
"id": "9111040_T8",
"type": "Protein",
"text": [
"RBP-Jkappa"
],
"offsets": [
[
787,
797
]
],
"normalized": []
},
{
"id": "9111040_T9",
"type": "Protein",
"text": [
"RBP-Jkappa"
],
"offsets": [
[
918,
928
]
],
"normalized": []
},
{
"id": "9111040_T10",
"type": "Protein",
"text": [
"NOTCH1"
],
"offsets": [
[
953,
959
]
],
"normalized": []
},
{
"id": "9111040_T11",
"type": "Protein",
"text": [
"RBP-Jkappa"
],
"offsets": [
[
1044,
1054
]
],
"normalized": []
},
{
"id": "9111040_T12",
"type": "Protein",
"text": [
"RBP-Jkappa"
],
"offsets": [
[
1190,
1200
]
],
"normalized": []
},
{
"id": "9111040_T13",
"type": "Protein",
"text": [
"NOTCH1"
],
"offsets": [
[
1834,
1840
]
],
"normalized": []
},
{
"id": "9111040_T14",
"type": "Protein",
"text": [
"RBP-Jkappa"
],
"offsets": [
[
1922,
1932
]
],
"normalized": []
},
{
"id": "9111040_T20",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
1571,
1578
]
],
"normalized": []
}
] | [
{
"id": "9111040_E1",
"type": "Binding",
"trigger": {
"text": [
"associate"
],
"offsets": [
[
137,
146
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9111040_T1"
},
{
"role": "Theme",
"ref_id": "9111040_T3"
}
]
},
{
"id": "9111040_E2",
"type": "Binding",
"trigger": {
"text": [
"bound"
],
"offsets": [
[
753,
758
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9111040_T8"
}
]
},
{
"id": "9111040_E3",
"type": "Positive_regulation",
"trigger": {
"text": [
"augments"
],
"offsets": [
[
1164,
1172
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9111040_E4"
}
]
},
{
"id": "9111040_E4",
"type": "Binding",
"trigger": {
"text": [
"association"
],
"offsets": [
[
1173,
1184
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9111040_T1"
},
{
"role": "Theme",
"ref_id": "9111040_T12"
}
]
},
{
"id": "9111040_E5",
"type": "Negative_regulation",
"trigger": {
"text": [
"decreased"
],
"offsets": [
[
1561,
1570
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9111040_E6"
}
]
},
{
"id": "9111040_E6",
"type": "Localization",
"trigger": {
"text": [
"localization"
],
"offsets": [
[
1579,
1591
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9111040_T1"
},
{
"role": "AtLoc",
"ref_id": "9111040_T20"
}
]
},
{
"id": "9111040_E7",
"type": "Binding",
"trigger": {
"text": [
"association"
],
"offsets": [
[
1905,
1916
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9111040_T14"
}
]
}
] | [] | [] |
1372388 | 1372388 | [
{
"id": "1372388__text",
"type": "abstract",
"text": [
"A lymphoid cell-specific nuclear factor containing c-Rel-like proteins preferentially interacts with interleukin-6 kappa B-related motifs whose activities are repressed in lymphoid cells. \nThe proto-oncoprotein c-Rel is a member of the nuclear factor kappa B transcription factor family, which includes the p50 and p65 subunits of nuclear factor kappa B. We show here that c-Rel binds to kappa B sites as homodimers as well as heterodimers with p50. These homodimers and heterodimers show distinct DNA-binding specificities and affinities for various kappa B motifs. In particular, the c-Rel homodimer has a high affinity for interleukin-6 (IL-6) and beta interferon kappa B sites. In spite of its association with p50 in vitro, however, we found a lymphoid cell-specific nuclear factor in vivo that contains c-Rel but not p50 epitopes; this factor, termed IL-6 kappa B binding factor II, appears to contain the c-Rel homodimer and preferentially recognizes several IL-6 kappa B-related kappa B motifs. Although it has been previously shown that the IL-6 kappa B motif functions as a potent IL-1/tumor necrosis factor-responsive element in nonlymphoid cells, its activity was found to be repressed in lymphoid cells such as a Jurkat T-cell line. We also present evidence that IL-6 kappa B binding factor II functions as a repressor specific for IL-6 kappa B-related kappa B motifs in lymphoid cells. "
],
"offsets": [
[
0,
1400
]
]
}
] | [
{
"id": "1372388_T1",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
51,
56
]
],
"normalized": []
},
{
"id": "1372388_T2",
"type": "Protein",
"text": [
"interleukin-6"
],
"offsets": [
[
101,
114
]
],
"normalized": []
},
{
"id": "1372388_T3",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
211,
216
]
],
"normalized": []
},
{
"id": "1372388_T4",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
373,
378
]
],
"normalized": []
},
{
"id": "1372388_T5",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
445,
448
]
],
"normalized": []
},
{
"id": "1372388_T6",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
586,
591
]
],
"normalized": []
},
{
"id": "1372388_T7",
"type": "Protein",
"text": [
"interleukin-6"
],
"offsets": [
[
626,
639
]
],
"normalized": []
},
{
"id": "1372388_T8",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
641,
645
]
],
"normalized": []
},
{
"id": "1372388_T9",
"type": "Protein",
"text": [
"beta interferon"
],
"offsets": [
[
651,
666
]
],
"normalized": []
},
{
"id": "1372388_T10",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
715,
718
]
],
"normalized": []
},
{
"id": "1372388_T11",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
809,
814
]
],
"normalized": []
},
{
"id": "1372388_T12",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
823,
826
]
],
"normalized": []
},
{
"id": "1372388_T13",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
857,
861
]
],
"normalized": []
},
{
"id": "1372388_T14",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
912,
917
]
],
"normalized": []
},
{
"id": "1372388_T15",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
966,
970
]
],
"normalized": []
},
{
"id": "1372388_T16",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1050,
1054
]
],
"normalized": []
},
{
"id": "1372388_T17",
"type": "Protein",
"text": [
"tumor necrosis factor"
],
"offsets": [
[
1096,
1117
]
],
"normalized": []
},
{
"id": "1372388_T18",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1276,
1280
]
],
"normalized": []
},
{
"id": "1372388_T19",
"type": "Protein",
"text": [
"IL-6"
],
"offsets": [
[
1345,
1349
]
],
"normalized": []
},
{
"id": "1372388_T26",
"type": "Entity",
"text": [
"kappa B sites"
],
"offsets": [
[
667,
680
]
],
"normalized": []
}
] | [
{
"id": "1372388_E1",
"type": "Binding",
"trigger": {
"text": [
"binds"
],
"offsets": [
[
379,
384
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T4"
}
]
},
{
"id": "1372388_E2",
"type": "Binding",
"trigger": {
"text": [
"homodimers"
],
"offsets": [
[
405,
415
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T4"
}
]
},
{
"id": "1372388_E3",
"type": "Binding",
"trigger": {
"text": [
"heterodimers"
],
"offsets": [
[
427,
439
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T4"
},
{
"role": "Theme",
"ref_id": "1372388_T5"
}
]
},
{
"id": "1372388_E4",
"type": "Binding",
"trigger": {
"text": [
"binding specificities"
],
"offsets": [
[
502,
523
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T4"
}
]
},
{
"id": "1372388_E5",
"type": "Binding",
"trigger": {
"text": [
"affinities"
],
"offsets": [
[
528,
538
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T4"
}
]
},
{
"id": "1372388_E6",
"type": "Binding",
"trigger": {
"text": [
"high affinity"
],
"offsets": [
[
608,
621
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T6"
},
{
"role": "Theme",
"ref_id": "1372388_T9"
},
{
"role": "Site",
"ref_id": "1372388_T26"
}
]
},
{
"id": "1372388_E7",
"type": "Binding",
"trigger": {
"text": [
"high affinity"
],
"offsets": [
[
608,
621
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T6"
},
{
"role": "Theme",
"ref_id": "1372388_T8"
},
{
"role": "Site",
"ref_id": "1372388_T26"
}
]
},
{
"id": "1372388_E8",
"type": "Binding",
"trigger": {
"text": [
"association"
],
"offsets": [
[
698,
709
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T10"
},
{
"role": "Theme",
"ref_id": "1372388_T13"
}
]
},
{
"id": "1372388_E9",
"type": "Binding",
"trigger": {
"text": [
"association"
],
"offsets": [
[
698,
709
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T10"
}
]
},
{
"id": "1372388_E10",
"type": "Binding",
"trigger": {
"text": [
"recognizes"
],
"offsets": [
[
947,
957
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1372388_T13"
}
]
}
] | [
{
"id": "1372388_1",
"entity_ids": [
"1372388_T7",
"1372388_T8"
]
}
] | [] |
9180266 | 9180266 | [
{
"id": "9180266__text",
"type": "abstract",
"text": [
"Transcriptional activity and constitutive nuclear localization of the ETS protein Elf-1. \nElf-1 is a lymphoid-specific transcription factor that belongs to the ETS protein family. It can bind to DNA target sequences within a variety of cytokine genes. We demonstrate that Elf-1 is constitutively localized in the nucleus which is dependent on the presence of amino acids 86-265. Analysis of Gal4-Elf-1 fusion proteins revealed that the N-terminal 86 amino acids of Elf-1 contain a transcriptional activation domain, the activity of which is attenuated by an internal repression domain. Furthermore, Elf-1 interacts specifically with the E74 target sequence and can stimulate transcription driven by the E74 site independent of mitogenic signaling. Thus, Elf-1 is able to stimulate gene transcription which may be required for the development and activity of lymphocytes. "
],
"offsets": [
[
0,
871
]
]
}
] | [
{
"id": "9180266_T1",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
82,
87
]
],
"normalized": []
},
{
"id": "9180266_T2",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
90,
95
]
],
"normalized": []
},
{
"id": "9180266_T3",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
272,
277
]
],
"normalized": []
},
{
"id": "9180266_T4",
"type": "Protein",
"text": [
"Gal4"
],
"offsets": [
[
391,
395
]
],
"normalized": []
},
{
"id": "9180266_T5",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
396,
401
]
],
"normalized": []
},
{
"id": "9180266_T6",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
465,
470
]
],
"normalized": []
},
{
"id": "9180266_T7",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
599,
604
]
],
"normalized": []
},
{
"id": "9180266_T8",
"type": "Protein",
"text": [
"Elf-1"
],
"offsets": [
[
754,
759
]
],
"normalized": []
},
{
"id": "9180266_T9",
"type": "Entity",
"text": [
"nuclear"
],
"offsets": [
[
42,
49
]
],
"normalized": []
},
{
"id": "9180266_T13",
"type": "Entity",
"text": [
"nucleus"
],
"offsets": [
[
313,
320
]
],
"normalized": []
}
] | [
{
"id": "9180266_E1",
"type": "Localization",
"trigger": {
"text": [
"localization"
],
"offsets": [
[
50,
62
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "9180266_T1"
},
{
"role": "AtLoc",
"ref_id": "9180266_T9"
}
]
},
{
"id": "9180266_E2",
"type": "Binding",
"trigger": {
"text": [
"bind"
],
"offsets": [
[
187,
191
]
]
},
"arguments": [
{
"role": "Theme",
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8635523 | 8635523 | [
{
"id": "8635523__text",
"type": "abstract",
"text": [
"Reversible differentiation of human monoblastic leukemia U937 cells by ML-9, an inhibitor of myosin light chain kinase. \nHuman monoblastic leukemia U937 cells are induced to differentiate into monocytes and macrophages by various agents. We have shown that 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9), an inhibitor of myosin light chain kinase, induces differentiation of monocytoid leukemia cell lines U937 and THP-1 but not of myeloblastic leukemic ML-1 cell or erythroleukemia K562 cells. In the present study, we further analyzed the effect of ML-9 in comparison with that of 1 alpha, 25-dihydroxyvitamin D3 (VD3) a typical inducer of monocytic differentiation. ML-9 induced nitroblue tetrazolium (NBT)-reducing activity of U937 cell more rapidly than VD3: This differentiation marker was induced significantly after incubation with ML-9 and VD3 for 4 hours and 1 day, respectively. ML-9 also induced alpha-naphthyl acetate esterase (ANAE) activity, another monocytic differentiation marker, more rapidly than VD3. The maximum levels of these markers induced by ML-9 were comparable to those induced by VD3, but after removal of ML-9 from the medium by washing the cells, the expressions of theses markers decreased within 4 hours and reached basal levels in 1 day, indicating that ML-9's induction of expression of differentiation-associated phenotypes was reversible. The growth inhibition of U937 cells by ML-9 was also reversible. Similar effects were observed in another line of human monoblastic cells, THP-1. ML-9 had little or no effect on the morphology of U937 cells but increased the expression of monocyte-macrophage lineage-associated surface antigen, CD14, to some extent. Irreversible terminal differentiation induced by VD3 is associated with down regulation of the expression of c-myc and upregulation of the expression of c-fos and c-jun, but ML-9 did not affect the expression of these oncogenes appreciably. ML-9-induced differentiation was also reversible when the cells were cultured with cultured with ML-9 plus an anti-cancer drug such as 1-beta-D-arabino-furanosylcytosine or daunomycin. it became irreversible, however, upon simultaneous treatment with dexamethasone and transforming growth factor-beta 1 (TGF-beta 1), which did not induce differentiation of U937 cells but caused growth arrest of the cells in the G0/G1 phase of the cell cycle. These results suggest that ML-9 should be useful for studying the mechanisms of monocytic differentiation. "
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] | [] |
9334193 | 9334193 | [
{
"id": "9334193__text",
"type": "abstract",
"text": [
"Monochloramine inhibits phorbol ester-inducible neutrophil respiratory burst activation and T cell interleukin-2 receptor expression by inhibiting inducible protein kinase C activity. \nMonochloramine derivatives are long lived physiological oxidants produced by neutrophils during the respiratory burst. The effects of chemically prepared monochloramine (NH2Cl) on protein kinase C (PKC) and PKC-mediated cellular responses were studied in elicited rat peritoneal neutrophils and human Jurkat T cells. Neutrophils pretreated with NH2Cl (30-50 microM) showed a marked decrease in the respiratory burst activity induced by phorbol 12-myristate 13-acetate (PMA), which is a potent PKC activator. These cells, however, were viable and showed a complete respiratory burst upon arachidonic acid stimulation, which induces the respiratory burst by a PKC-independent mechanism. The NH2Cl-treated neutrophils showed a decrease in both PKC activity and PMA-induced phosphorylation of a 47-kDa protein, which corresponds to the cytosolic factor of NADPH oxidase, p47(phox). Jurkat T cells pretreated with NH2Cl (20-70 microM) showed a decrease in the expression of the interleukin-2 receptor alpha chain following PMA stimulation. This was also accompanied by a decrease in both PKC activity and nuclear transcription factor-kappaB activation, also without loss of cell viability. These results show that NH2Cl inhibits PKC-mediated cellular responses through inhibition of the inducible PKC activity. "
],
"offsets": [
[
0,
1491
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]
}
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1158,
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"role": "Theme",
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] | [] | [] |
9440546 | 9440546 | [
{
"id": "9440546__text",
"type": "abstract",
"text": [
"Cellular and molecular mechanisms of IL-5 synthesis in atopic diseases: a study with allergen-specific human helper T cells. \nBACKGROUND: Cytokines produced by helper T cells are intimately involved in chronic allergic diseases associated with eosinophilic inflammation. OBJECTIVE: We investigated the production of IL-5, a potent growth factor and chemotactic factor for eosinophils, by CD4+ T lymphocytes in patients with asthma. METHODS: Allergen-specific T cell clones and T cell hybridomas were established from the peripheral blood lymphocytes of patients with asthma, and the responses to various stimuli were determined. RESULTS: After nonspecific stimulation, IL-5 production by CD4+ T cells from both atopic and nonatopic subjects with asthma was significantly enhanced compared with that by cells from healthy controls. Peripheral blood mononuclear cells from atopic asthma patients both proliferated and produced IL-5 after incubation with mite allergen, suggesting that mite-specific helper T cells were involved in the eosinophilic inflammation of atopic asthma. A human IL-5 promoter/enhancer luciferase gene construct transfected into IL-5-producing T cell clones was clearly transcribed after stimulation, indicating that the 515 base pair IL-5 gene segment upstream of the coding region was sufficient to respond to activating signals in human helper T cells. The same gene segment was not transcribed in IL-5-nonproducing T cell clones, suggesting that human T cell IL-5 synthesis is regulated at the transcriptional level. Experiments with T cell hybridomas confirmed these findings and suggested that a unique transcription factor may be essential for human IL-5 gene transcription. CONCLUSION: Enhanced IL-5 production by helper T cells seems to cause the eosinophilic inflammation of both atopic and nonatopic asthma. Elucidation of IL-5-specific regulatory mechanisms may facilitate the development of novel treatments for allergic diseases associated with eosinophilic inflammation. "
],
"offsets": [
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0,
2008
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]
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"role": "Theme",
"ref_id": "9440546_T11"
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}
] | [] | [] |
9144338 | 9144338 | [
{
"id": "9144338__text",
"type": "abstract",
"text": [
"Quantification of vitamin D receptor mRNA by competitive polymerase chain reaction in PBMC: lack of correspondence with common allelic variants. \nIt has been recently claimed that polymorphism for the vitamin D receptor (VDR) influences several aspects of calcium and bone metabolism. To evaluate the physiologic plausibility of these claims, we compared the abundance of the VDR mRNA in peripheral blood mononuclear cells (PBMCs) between different VDR genotypes using a quantitative reverse transcribed polymerase chain reaction-based method. The method is based on the coamplification of VDR cDNA and an internal standard consisting of known concentrations of a human VDR CDNA mutated at a BglII restriction site; the interassay coefficient of variation is 11%. To validate the method, we made use of earlier receptor binding studies indicating that normal human monocytes and activated, but not resting, lymphocytes expressed the VDR. The concentration of the VDR mRNA was 10(-8) to 10(-7) g/g of total RNA in cell-sorted monocytes and in in vitro activated lymphocytes, but only 10(-12) g/g of total mRNA in resting lymphocytes, establishing that the VDR mRNA determined by our method in PBMCs is due to constitutive expression in monocytes. Following an initial genotype screening of 85 normal volunteers by polymerase chain reaction or restriction fragment length polymorphism analysis, 14 individuals with the Bb genotype, 12 with the bb genotype, and 12 with the BB genotype were selected. The concentration of the VDR mRNA, corrected for the number of monocytes, was similar among the three genotype groups, as were the other variables examined: serum calcitriol, serum osteocalcin, and vertebral and hip bone density. We conclude that VDR polymorphism does not affect the abundance of the VDR mRNA. "
],
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[
0,
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{
"id": "9144338_1",
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"9144338_T3"
]
}
] | [] |
10329845 | 10329845 | [
{
"id": "10329845__text",
"type": "abstract",
"text": [
"Transcriptional control of the IL-5 gene by human helper T cells: IL-5 synthesis is regulated independently from IL-2 or IL-4 synthesis. \nBACKGROUND: IL-5 is fundamentally involved in eosinophilic inflammation. Control of IL-5 production may be effective for the management of allergic diseases. OBJECTIVE: We aimed to find the transcriptional mechanisms that regulate the IL-5 gene to selectively control IL-5 synthesis. METHODS: Allergen-specific T-cell clones and T-cell hybridomas were established from the peripheral blood lymphocytes of patients with asthma, and the transcriptional regulation of the IL-5 gene was investigated with transient transfection and electrophoretic mobility shift analysis. RESULTS: A human IL-5 promoter/enhancer-luciferase gene construct, pIL-5(-511)Luc, was transcribed on activation of IL-5-producing T-cell clones, but not IL-5-nonproducing clones. pIL-5(-511)Luc was transcribed by T-cell hybridomas derived from fusion between IL-5-producing T-cell clones and an IL-5 gene-nonexpressing T-cell line, but not by hybridomas derived from IL-5-nonproducing T-cell clones. IL-5 synthesis was not only induced by T-cell receptor stimulation but also by IL-2 receptor stimulation. Binding of NF-AT, NF-kappaB, and AP-1 was induced by T-cell receptor (TcR) stimulation, although there was no significant upregulation of binding by IL-2 stimulation. CONCLUSION: IL-5 synthesis by human helper T cells is regulated at the transcriptional level. A unique transcriptional mechanism distinct from those regulating the IL-2 or IL-4 genes seems to control the IL-5 gene. Selective regulation of IL-5 gene transcription may be useful for treating eosinophlic inflammation. "
],
"offsets": [
[
0,
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"role": "Theme",
"ref_id": "10329845_T1"
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}
] | [] | [] |
8642282 | 8642282 | [
{
"id": "8642282__text",
"type": "abstract",
"text": [
"A cell type-specific enhancer in the human B7.1 gene regulated by NF-kappaB. \nThe costimulatory molecule B7.1 provides a second signal critical for T cell activation. The distribution of this integral membrane protein is restricted to certain tissues where its level of expression is modulated by multiple exogenous stimuli. To identify the molecular basis for specificity and inducibility, the chromatin configuration of the human B7.1 gene was examined in intact nuclei from various cell types. The identification of a tissue-specific deoxyribonuclease I hypersensitive site approximately 3kb upstream of the transcription start site led to the characterization of a cell type-specific enhancer region. This 183-bp region was both cell type specific and responsive to two distinct stimuli, lipopolysaccharide and dibutyryl cAMP, known to regulate B7.1 expression. Deletional and site-directed mutagenesis revealed the presence of multiple functionally critical cis elements within this region, one of which was a nuclear factor (NF)-kappaB consensus sequence. In B7.1-positive B cells, this element bound several members of the NF-kappaB family, transcription factors already implicated in signal transduction pathways relevant to B7.1 expression. This is the first description, to our knowledge, of regulatory elements that control expression of a gene encoding a B7 costimulatory molecule. "
],
"offsets": [
[
0,
1394
]
]
}
] | [
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43,
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105,
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{
"id": "8642282_T5",
"type": "Protein",
"text": [
"B7.1"
],
"offsets": [
[
1065,
1069
]
],
"normalized": []
},
{
"id": "8642282_T6",
"type": "Protein",
"text": [
"B7.1"
],
"offsets": [
[
1233,
1237
]
],
"normalized": []
}
] | [
{
"id": "8642282_E1",
"type": "Regulation",
"trigger": {
"text": [
"regulated"
],
"offsets": [
[
53,
62
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8642282_T1"
}
]
},
{
"id": "8642282_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"distribution"
],
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[
171,
183
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8642282_T2"
}
]
},
{
"id": "8642282_E3",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
270,
280
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8642282_T2"
}
]
},
{
"id": "8642282_E4",
"type": "Regulation",
"trigger": {
"text": [
"modulated"
],
"offsets": [
[
284,
293
]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8642282_E3"
}
]
},
{
"id": "8642282_E5",
"type": "Regulation",
"trigger": {
"text": [
"regulate"
],
"offsets": [
[
840,
848
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8642282_E6"
}
]
},
{
"id": "8642282_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
854,
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]
]
},
"arguments": [
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"role": "Theme",
"ref_id": "8642282_T4"
}
]
},
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"id": "8642282_E7",
"type": "Gene_expression",
"trigger": {
"text": [
"positive"
],
"offsets": [
[
1070,
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]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8642282_T5"
}
]
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"id": "8642282_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
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1238,
1248
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8642282_T6"
}
]
}
] | [] | [] |
1520341 | 1520341 | [
{
"id": "1520341__text",
"type": "abstract",
"text": [
"Okadaic acid is a potent inducer of AP-1, NF-kappa B, and tumor necrosis factor-alpha in human B lymphocytes. \nTreatment of human B lymphocytes with an optimal concentration of okadaic acid, an inhibitor of phosphatases 1 and 2A, resulted in the induction of the transcription factor, AP-1 and a marked increase in NF-kappa B levels. In contrast, no effect on the levels of the octamer binding proteins, Oct-1 or Oct-2, were found. Since both AP-1 and NF-kappa B have been reported to be important in the induction of the tumor necrosis factor-alpha (TNF-alpha) gene we examined the effects of okadaic acid on TNF-alpha mRNA levels. Treatment with okadaic acid resulted in a striking increase in TNF-alpha mRNA transcripts within 1 h of stimulation and large amounts of TNF-alpha were released into the culture media. Although okadaic acid provides a potent inductive signal for AP-1 and NF-kappa B it did not induce either B cell proliferation or immunoglobulin secretion. "
],
"offsets": [
[
0,
974
]
]
}
] | [
{
"id": "1520341_T1",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
58,
85
]
],
"normalized": []
},
{
"id": "1520341_T2",
"type": "Protein",
"text": [
"phosphatases 1"
],
"offsets": [
[
207,
221
]
],
"normalized": []
},
{
"id": "1520341_T3",
"type": "Protein",
"text": [
"2A"
],
"offsets": [
[
226,
228
]
],
"normalized": []
},
{
"id": "1520341_T4",
"type": "Protein",
"text": [
"Oct-1"
],
"offsets": [
[
404,
409
]
],
"normalized": []
},
{
"id": "1520341_T5",
"type": "Protein",
"text": [
"Oct-2"
],
"offsets": [
[
413,
418
]
],
"normalized": []
},
{
"id": "1520341_T6",
"type": "Protein",
"text": [
"tumor necrosis factor-alpha"
],
"offsets": [
[
522,
549
]
],
"normalized": []
},
{
"id": "1520341_T7",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
551,
560
]
],
"normalized": []
},
{
"id": "1520341_T8",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
610,
619
]
],
"normalized": []
},
{
"id": "1520341_T9",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
696,
705
]
],
"normalized": []
},
{
"id": "1520341_T10",
"type": "Protein",
"text": [
"TNF-alpha"
],
"offsets": [
[
770,
779
]
],
"normalized": []
}
] | [
{
"id": "1520341_E1",
"type": "Positive_regulation",
"trigger": {
"text": [
"inducer"
],
"offsets": [
[
25,
32
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T1"
}
]
},
{
"id": "1520341_E2",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitor"
],
"offsets": [
[
194,
203
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T2"
}
]
},
{
"id": "1520341_E3",
"type": "Negative_regulation",
"trigger": {
"text": [
"inhibitor"
],
"offsets": [
[
194,
203
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T3"
}
]
},
{
"id": "1520341_E4",
"type": "Positive_regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
350,
356
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T4"
}
]
},
{
"id": "1520341_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"effect"
],
"offsets": [
[
350,
356
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T5"
}
]
},
{
"id": "1520341_E6",
"type": "Regulation",
"trigger": {
"text": [
"important"
],
"offsets": [
[
488,
497
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_E8"
}
]
},
{
"id": "1520341_E7",
"type": "Positive_regulation",
"trigger": {
"text": [
"important"
],
"offsets": [
[
488,
497
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_E8"
}
]
},
{
"id": "1520341_E8",
"type": "Gene_expression",
"trigger": {
"text": [
"induction"
],
"offsets": [
[
505,
514
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T7"
}
]
},
{
"id": "1520341_E9",
"type": "Regulation",
"trigger": {
"text": [
"effects"
],
"offsets": [
[
583,
590
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T8"
}
]
},
{
"id": "1520341_E10",
"type": "Positive_regulation",
"trigger": {
"text": [
"increase"
],
"offsets": [
[
684,
692
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T9"
}
]
},
{
"id": "1520341_E11",
"type": "Positive_regulation",
"trigger": {
"text": [
"large amounts"
],
"offsets": [
[
753,
766
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_E12"
},
{
"role": "Cause",
"ref_id": "1520341_E10"
}
]
},
{
"id": "1520341_E12",
"type": "Localization",
"trigger": {
"text": [
"released"
],
"offsets": [
[
785,
793
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "1520341_T10"
}
]
}
] | [
{
"id": "1520341_1",
"entity_ids": [
"1520341_T6",
"1520341_T7"
]
}
] | [] |
8602529 | 8602529 | [
{
"id": "8602529__text",
"type": "abstract",
"text": [
"A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p [see comments] \nTrapoxin is a microbially derived cyclotetrapeptide that inhibits histone deacetylation in vivo and causes mammalian cells to arrest in the cell cycle. A trapoxin affinity matrix was used to isolate two nuclear proteins that copurified with histone deacetylase activity. Both proteins were identified by peptide microsequencing, and a complementary DNA encoding the histone deacetylase catalytic subunit (HD1) was cloned from a human Jurkat T cell library. As the predicted protein is very similar to the yeast transcriptional regulator Rpd3p, these results support a role for histone deacetylase as a key regulator of eukaryotic transcription. "
],
"offsets": [
[
0,
746
]
]
}
] | [
{
"id": "8602529_T1",
"type": "Protein",
"text": [
"Rpd3p"
],
"offsets": [
[
79,
84
]
],
"normalized": []
},
{
"id": "8602529_T2",
"type": "Protein",
"text": [
"HD1"
],
"offsets": [
[
506,
509
]
],
"normalized": []
},
{
"id": "8602529_T3",
"type": "Protein",
"text": [
"Rpd3p"
],
"offsets": [
[
638,
643
]
],
"normalized": []
}
] | [] | [] | [] |
8799177 | 8799177 | [
{
"id": "8799177__text",
"type": "abstract",
"text": [
"Epstein-Barr viral latency is disrupted by the immediate-early BRLF1 protein through a cell-specific mechanism. \nEpstein-Barr virus (EBV), the causative agent of infectious mononucleosis, is a human herpesvirus associated with epithelial cell malignancies (nasopharyngeal carcinoma) as well as B-cell malignancies. Understanding how viral latency is disrupted is a central issue in herpesvirus biology. Epithelial cells are the major site of lytic EBV replication within the human host, and viral reactivation occurs in EBV-associated nasopharyngeal carcinomas. It is known that expression of a single viral immediate-early protein, BZLF1, is sufficient to initiate the switch from latent to lytic infection in B cells. Cellular regulation of BZLF1 transcription is therefore thought to play a key role in regulating the stringency of viral latency. Here we show that, unexpectedly, expression of another viral immediate-early protein, BRLF1, can disrupt viral latency in an epithelial cell-specific fashion. Therefore, the mechanisms leading to disruption of EBV latency appear to be cell-type specific. "
],
"offsets": [
[
0,
1105
]
]
}
] | [
{
"id": "8799177_T1",
"type": "Protein",
"text": [
"BRLF1"
],
"offsets": [
[
63,
68
]
],
"normalized": []
},
{
"id": "8799177_T2",
"type": "Protein",
"text": [
"BZLF1"
],
"offsets": [
[
633,
638
]
],
"normalized": []
},
{
"id": "8799177_T3",
"type": "Protein",
"text": [
"BZLF1"
],
"offsets": [
[
743,
748
]
],
"normalized": []
},
{
"id": "8799177_T4",
"type": "Protein",
"text": [
"BRLF1"
],
"offsets": [
[
936,
941
]
],
"normalized": []
}
] | [
{
"id": "8799177_E1",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
579,
589
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8799177_T2"
}
]
},
{
"id": "8799177_E2",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
729,
739
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8799177_E3"
}
]
},
{
"id": "8799177_E3",
"type": "Transcription",
"trigger": {
"text": [
"transcription"
],
"offsets": [
[
749,
762
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8799177_T3"
}
]
},
{
"id": "8799177_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
883,
893
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "8799177_T4"
}
]
}
] | [] | [] |
7929104 | 7929104 | [
{
"id": "7929104__text",
"type": "abstract",
"text": [
"Regulation of interleukin-2 receptor alpha chain expression and nuclear factor.kappa B activation by protein kinase C in T lymphocytes. Autocrine role of tumor necrosis factor alpha. \nThe regulation of interleukin-2 receptor alpha chain (IL-2R alpha) expression and nuclear factor (NF) activation by protein kinase C (PKC) in resting T cells, has been studied. Treatment of human resting T cells with phorbol esters strongly induced the expression of IL-2R alpha and the activation of NF.kappa B. This activation was due to the translocation of p65 and c-Rel NF.kappa B proteins from cytoplasmic stores to the nucleus, where they bound the kappa B sequence of the IL-2R alpha promoter either as p50.p65 or as p50.c-Rel heterodimers. Interestingly, all of those events were largely indirect and mediated by endogenously secreted tumor necrosis factor alpha (TNF alpha), as they were strongly inhibited by a neutralizing anti-TNF alpha monoclonal antibody. Furthermore, cyclosporin A, which blocked TNF alpha production induced by PKC, strongly inhibited IL-2R alpha and NF.kappa B activation. The addition of either TNF alpha or IL-2 partially recovered cyclosporin A-induced IL-2R alpha inhibition, but only TNF alpha completely recovered NF.kappa B activation. Those results indicate that, in resting T cells, PKC activation has only a triggering role, whereas the endogenously secreted TNF alpha plays an essential role in the quantitative control of the expression of IL-2R alpha chain or NF.kappa B activation. "
],
"offsets": [
[
0,
1515
]
]
}
] | [
{
"id": "7929104_T1",
"type": "Protein",
"text": [
"interleukin-2 receptor alpha chain"
],
"offsets": [
[
14,
48
]
],
"normalized": []
},
{
"id": "7929104_T2",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
154,
181
]
],
"normalized": []
},
{
"id": "7929104_T3",
"type": "Protein",
"text": [
"interleukin-2 receptor alpha chain"
],
"offsets": [
[
202,
236
]
],
"normalized": []
},
{
"id": "7929104_T4",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
238,
249
]
],
"normalized": []
},
{
"id": "7929104_T5",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
451,
462
]
],
"normalized": []
},
{
"id": "7929104_T6",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
545,
548
]
],
"normalized": []
},
{
"id": "7929104_T7",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
553,
558
]
],
"normalized": []
},
{
"id": "7929104_T8",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
664,
675
]
],
"normalized": []
},
{
"id": "7929104_T9",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
695,
698
]
],
"normalized": []
},
{
"id": "7929104_T10",
"type": "Protein",
"text": [
"p65"
],
"offsets": [
[
699,
702
]
],
"normalized": []
},
{
"id": "7929104_T11",
"type": "Protein",
"text": [
"p50"
],
"offsets": [
[
709,
712
]
],
"normalized": []
},
{
"id": "7929104_T12",
"type": "Protein",
"text": [
"c-Rel"
],
"offsets": [
[
713,
718
]
],
"normalized": []
},
{
"id": "7929104_T13",
"type": "Protein",
"text": [
"tumor necrosis factor alpha"
],
"offsets": [
[
828,
855
]
],
"normalized": []
},
{
"id": "7929104_T14",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
857,
866
]
],
"normalized": []
},
{
"id": "7929104_T15",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
924,
933
]
],
"normalized": []
},
{
"id": "7929104_T16",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
997,
1006
]
],
"normalized": []
},
{
"id": "7929104_T17",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
1053,
1064
]
],
"normalized": []
},
{
"id": "7929104_T18",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
1115,
1124
]
],
"normalized": []
},
{
"id": "7929104_T19",
"type": "Protein",
"text": [
"IL-2"
],
"offsets": [
[
1128,
1132
]
],
"normalized": []
},
{
"id": "7929104_T20",
"type": "Protein",
"text": [
"IL-2R alpha"
],
"offsets": [
[
1175,
1186
]
],
"normalized": []
},
{
"id": "7929104_T21",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
1208,
1217
]
],
"normalized": []
},
{
"id": "7929104_T22",
"type": "Protein",
"text": [
"TNF alpha"
],
"offsets": [
[
1388,
1397
]
],
"normalized": []
},
{
"id": "7929104_T23",
"type": "Protein",
"text": [
"IL-2R alpha chain"
],
"offsets": [
[
1471,
1488
]
],
"normalized": []
},
{
"id": "7929104_T31",
"type": "Entity",
"text": [
"nucleus"
],
"offsets": [
[
610,
617
]
],
"normalized": []
}
] | [
{
"id": "7929104_E1",
"type": "Regulation",
"trigger": {
"text": [
"Regulation"
],
"offsets": [
[
0,
10
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7929104_E2"
}
]
},
{
"id": "7929104_E2",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
49,
59
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7929104_T1"
}
]
},
{
"id": "7929104_E3",
"type": "Regulation",
"trigger": {
"text": [
"regulation"
],
"offsets": [
[
188,
198
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7929104_E4"
}
]
},
{
"id": "7929104_E4",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
251,
261
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7929104_T4"
}
]
},
{
"id": "7929104_E5",
"type": "Positive_regulation",
"trigger": {
"text": [
"induced"
],
"offsets": [
[
425,
432
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7929104_E6"
}
]
},
{
"id": "7929104_E6",
"type": "Gene_expression",
"trigger": {
"text": [
"expression"
],
"offsets": [
[
437,
447
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7929104_T5"
}
]
},
{
"id": "7929104_E7",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
528,
541
]
]
},
"arguments": [
{
"role": "Theme",
"ref_id": "7929104_T6"
},
{
"role": "ToLoc",
"ref_id": "7929104_T31"
}
]
},
{
"id": "7929104_E8",
"type": "Localization",
"trigger": {
"text": [
"translocation"
],
"offsets": [
[
528,
541
]
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] | [] |
1533884 | 1533884 | [
{
"id": "1533884__text",
"type": "abstract",
"text": [
"Activation of the human immunodeficiency virus type 1 enhancer is not dependent on NFAT-1. \nThe function of a putative NFAT-1 site in the human immunodeficiency virus type 1 enhancer has been analyzed. Activation by the T-cell antigen receptor is minimal in Jurkat cells and is mediated by the kappa B sites. The putative NFAT-1 region is not required for the response to anti-CD3 or to mitogens in T-cell, B-cell, or monocyte/macrophage leukemia lines, nor is it a cis-acting negative regulatory element. "
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] | [] | [] | [] |