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http://purl.uniprot.org/citations/10823840http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10823840http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10823840http://www.w3.org/2000/01/rdf-schema#comment"Activation of the transcription factor NF-kappaB is controlled at two levels in resting T cells: an initial activation induced by the triggering of the TcR.CD3 complex and a second phase controlled by paracrine- or autocrine-secreted TNFalpha. The initial phase is regulated by p65 (RelA), whereas the second one is mainly dependent on c-Rel. We describe here a mutant clone, D6, derived from the parental T lymphoblastic line Jurkat that fails to activate NF-kappaB upon TNFalpha stimulation. This clone had no alteration in tumor necrosis factor-alpha (TNFalpha) signaling pathways nor in IkappaBalpha, -beta, or -epsilon expression and degradation. However, TNFalpha induced an exacerbated apoptotic response in this clone compared with Jurkat cells. This mutant clone showed a defect in the intermediate-late translocation of c-Rel to the nucleus promoted by TNFalpha stimulation, whereas early translocation is not affected. Activation or translocation of p65-containing complexes was not altered in this mutant clone. Sequencing of the c-Rel gene from this clone revealed a mutation of Ser-471 to Asn in the transactivation domain. The mutant S471N transactivation domain fused to the Gal4 DNA binding domain could not be activated by TNFalpha, unlike the wild type. Moreover, the overexpression of the mutant protein c-Rel S471N into Jurkat cells abolished TNFalpha-induced NF-kappaB activity, thus demonstrating that this mutation is responsible for the failure of TNFalpha stimulation of NF-kappaB. Moreover, extracts from TNFalpha-stimulated Jurkat cells phosphorylated in vitro recombinant wild type GST-c-Rel 464-481 but not the GST-c-Rel mutant. Thus, TNFalpha-induced phosphorylation of Ser-471 seems to be absolutely necessary for TNFalpha activation of c-Rel."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m909396199"xsd:string
http://purl.uniprot.org/citations/10823840http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m909396199"xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/author"Fresno M."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/author"Fresno M."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/author"Martin A.G."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/author"Martin A.G."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/pages"24383-24391"xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/pages"24383-24391"xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/title"Tumor necrosis factor-alpha activation of NF-kappa B requires the phosphorylation of Ser-471 in the transactivation domain of c-Rel."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/title"Tumor necrosis factor-alpha activation of NF-kappa B requires the phosphorylation of Ser-471 in the transactivation domain of c-Rel."xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/volume"275"xsd:string
http://purl.uniprot.org/citations/10823840http://purl.uniprot.org/core/volume"275"xsd:string
http://purl.uniprot.org/citations/10823840http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10823840
http://purl.uniprot.org/citations/10823840http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10823840
http://purl.uniprot.org/citations/10823840http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/10823840
http://purl.uniprot.org/citations/10823840http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/10823840
http://purl.uniprot.org/uniprot/Q04864http://purl.uniprot.org/core/citationhttp://purl.uniprot.org/citations/10823840
http://purl.uniprot.org/uniprot/Q04864#attribution-E29604477CD1D9F5C2E4375CEB37910Dhttp://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/10823840