PubMed:10022897 JSON TXT

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PMID_GLOBAL

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":312,"end":323},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0000605"}],"text":"Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment.\nFas (CD95) and Fas ligand (CD95L) are an interacting receptor-ligand pair required for immune homeostasis. Lymphocyte activation results in the upregulation of Fas expression and the acquisition of sensitivity to FasL-mediated apoptosis. Although Fas upregulation is central to the preservation of immunologic tolerance, little is known about the molecular machinery underlying this process. To investigate the events involved in activation-induced Fas upregulation, we have examined mRNA accumulation, fas promoter activity, and protein expression in the Jurkat T-cell line treated with phorbol myristate acetate and ionomycin (P/I), pharmacological mimics of T-cell receptor activation. Although resting Jurkat cells express Fas, Fas mRNA was induced approximately 10-fold in 2 h upon P/I stimulation. Using sequential deletion mutants of the human fas promoter in transient transfection assays, we identified a 47-bp sequence (positions -306 to -260 relative to the ATG) required for activation-driven fas upregulation. Sequence analysis revealed the presence of a previously unrecognized composite binding site for both the Sp1 and NF-kappaB transcription factors at positions -295 to -286. Electrophoretic mobility shift assay (EMSA) and supershift analyses of this region documented constitutive binding of Sp1 in unactivated nuclear extracts and inducible binding of p50-p65 NF-kappaB heterodimers after P/I activation. Sp1 and NF-kappaB transcription factor binding was shown to be mutually exclusive by EMSA displacement studies with purified recombinant Sp1 and recombinant p50. The functional contribution of the kappaB-Sp1 composite site in P/I-inducible fas promoter activation was verified by using kappaB-Sp1 concatamers (-295 to -286) in a thymidine kinase promoter-driven reporter construct and native promoter constructs in Jurkat cells overexpressing IkappaB-alpha. Site-directed mutagenesis of the critical guanine nucleotides in the kappaB-Sp1 element documented the essential role of this site in activation-dependent fas promoter induction."}

jnlpba-st-training

genia-medco-coref

{"project":"genia-medco-coref","denotations":[{"id":"C1","span":{"begin":51,"end":73},"obj":"NP"},{"id":"C2","span":{"begin":114,"end":124},"obj":"NP"},{"id":"C3","span":{"begin":254,"end":288},"obj":"NP"},{"id":"C4","span":{"begin":361,"end":377},"obj":"NP"},{"id":"C5","span":{"begin":492,"end":504},"obj":"NP"},{"id":"C6","span":{"begin":544,"end":579},"obj":"NP"},{"id":"C7","span":{"begin":702,"end":747},"obj":"NP"},{"id":"C8","span":{"begin":749,"end":801},"obj":"NP"},{"id":"C9","span":{"begin":841,"end":844},"obj":"NP"},{"id":"C10","span":{"begin":955,"end":977},"obj":"NP"},{"id":"C11","span":{"begin":1101,"end":1135},"obj":"NP"},{"id":"C12","span":{"begin":1285,"end":1307},"obj":"NP"},{"id":"C13","span":{"begin":1309,"end":1352},"obj":"NP"},{"id":"C14","span":{"begin":1380,"end":1391},"obj":"NP"},{"id":"C15","span":{"begin":1626,"end":1630},"obj":"NP"},{"id":"C16","span":{"begin":1734,"end":1763},"obj":"NP"},{"id":"C17","span":{"begin":2120,"end":2129},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-ident","subj":"C4","obj":"C3"},{"id":"R2","pred":"coref-ident","subj":"C5","obj":"C4"},{"id":"R3","pred":"coref-ident","subj":"C6","obj":"C5"},{"id":"R4","pred":"coref-appos","subj":"C8","obj":"C7"},{"id":"R5","pred":"coref-ident","subj":"C9","obj":"C2"},{"id":"R6","pred":"coref-ident","subj":"C10","obj":"C1"},{"id":"R7","pred":"coref-ident","subj":"C11","obj":"C6"},{"id":"R8","pred":"coref-ident","subj":"C14","obj":"C12"},{"id":"R9","pred":"coref-ident","subj":"C15","obj":"C13"},{"id":"R10","pred":"coref-ident","subj":"C17","obj":"C16"}],"text":"Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment.\nFas (CD95) and Fas ligand (CD95L) are an interacting receptor-ligand pair required for immune homeostasis. Lymphocyte activation results in the upregulation of Fas expression and the acquisition of sensitivity to FasL-mediated apoptosis. Although Fas upregulation is central to the preservation of immunologic tolerance, little is known about the molecular machinery underlying this process. To investigate the events involved in activation-induced Fas upregulation, we have examined mRNA accumulation, fas promoter activity, and protein expression in the Jurkat T-cell line treated with phorbol myristate acetate and ionomycin (P/I), pharmacological mimics of T-cell receptor activation. Although resting Jurkat cells express Fas, Fas mRNA was induced approximately 10-fold in 2 h upon P/I stimulation. Using sequential deletion mutants of the human fas promoter in transient transfection assays, we identified a 47-bp sequence (positions -306 to -260 relative to the ATG) required for activation-driven fas upregulation. Sequence analysis revealed the presence of a previously unrecognized composite binding site for both the Sp1 and NF-kappaB transcription factors at positions -295 to -286. Electrophoretic mobility shift assay (EMSA) and supershift analyses of this region documented constitutive binding of Sp1 in unactivated nuclear extracts and inducible binding of p50-p65 NF-kappaB heterodimers after P/I activation. Sp1 and NF-kappaB transcription factor binding was shown to be mutually exclusive by EMSA displacement studies with purified recombinant Sp1 and recombinant p50. The functional contribution of the kappaB-Sp1 composite site in P/I-inducible fas promoter activation was verified by using kappaB-Sp1 concatamers (-295 to -286) in a thymidine kinase promoter-driven reporter construct and native promoter constructs in Jurkat cells overexpressing IkappaB-alpha. Site-directed mutagenesis of the critical guanine nucleotides in the kappaB-Sp1 element documented the essential role of this site in activation-dependent fas promoter induction."}

pubmed-sentences-benchmark

{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":113},"obj":"Sentence"},{"id":"S2","span":{"begin":114,"end":220},"obj":"Sentence"},{"id":"S3","span":{"begin":221,"end":351},"obj":"Sentence"},{"id":"S4","span":{"begin":352,"end":505},"obj":"Sentence"},{"id":"S5","span":{"begin":506,"end":802},"obj":"Sentence"},{"id":"S6","span":{"begin":803,"end":917},"obj":"Sentence"},{"id":"S7","span":{"begin":918,"end":1136},"obj":"Sentence"},{"id":"S8","span":{"begin":1137,"end":1308},"obj":"Sentence"},{"id":"S9","span":{"begin":1309,"end":1540},"obj":"Sentence"},{"id":"S10","span":{"begin":1541,"end":1702},"obj":"Sentence"},{"id":"S11","span":{"begin":1703,"end":1998},"obj":"Sentence"},{"id":"S12","span":{"begin":1999,"end":2177},"obj":"Sentence"}],"text":"Activation-dependent transcriptional regulation of the human Fas promoter requires NF-kappaB p50-p65 recruitment.\nFas (CD95) and Fas ligand (CD95L) are an interacting receptor-ligand pair required for immune homeostasis. Lymphocyte activation results in the upregulation of Fas expression and the acquisition of sensitivity to FasL-mediated apoptosis. Although Fas upregulation is central to the preservation of immunologic tolerance, little is known about the molecular machinery underlying this process. To investigate the events involved in activation-induced Fas upregulation, we have examined mRNA accumulation, fas promoter activity, and protein expression in the Jurkat T-cell line treated with phorbol myristate acetate and ionomycin (P/I), pharmacological mimics of T-cell receptor activation. Although resting Jurkat cells express Fas, Fas mRNA was induced approximately 10-fold in 2 h upon P/I stimulation. Using sequential deletion mutants of the human fas promoter in transient transfection assays, we identified a 47-bp sequence (positions -306 to -260 relative to the ATG) required for activation-driven fas upregulation. Sequence analysis revealed the presence of a previously unrecognized composite binding site for both the Sp1 and NF-kappaB transcription factors at positions -295 to -286. Electrophoretic mobility shift assay (EMSA) and supershift analyses of this region documented constitutive binding of Sp1 in unactivated nuclear extracts and inducible binding of p50-p65 NF-kappaB heterodimers after P/I activation. Sp1 and NF-kappaB transcription factor binding was shown to be mutually exclusive by EMSA displacement studies with purified recombinant Sp1 and recombinant p50. The functional contribution of the kappaB-Sp1 composite site in P/I-inducible fas promoter activation was verified by using kappaB-Sp1 concatamers (-295 to -286) in a thymidine kinase promoter-driven reporter construct and native promoter constructs in Jurkat cells overexpressing IkappaB-alpha. Site-directed mutagenesis of the critical guanine nucleotides in the kappaB-Sp1 element documented the essential role of this site in activation-dependent fas promoter induction."}

GENIAcorpus