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http://purl.uniprot.org/citations/20622870http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20622870http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20622870http://www.w3.org/2000/01/rdf-schema#comment"We describe a genome-wide gain-of-function screen for regulators of NF-kappaB, and identify Rap1 (Trf2IP), as an essential modulator of NF-kappaB-mediated pathways. NF-kappaB is induced by ectopic expression of Rap1, whereas its activity is inhibited by Rap1 depletion. In addition to localizing on telomeres, mammalian Rap1 forms a complex with IKKs (IkappaB kinases), and is crucial for the ability of IKKs to be recruited to, and phosphorylate, the p65 subunit of NF-kappaB to make it transcriptionally competent. Rap1-mutant mice display defective NF-kappaB activation and are resistant to endotoxic shock. Furthermore, levels of Rap1 are positively regulated by NF-kappaB, and human breast cancers with NF-kappaB hyperactivity show elevated levels of cytoplasmic Rap1. Similar to inhibiting NF-kappaB, knockdown of Rap1 sensitizes breast cancer cells to apoptosis. These results identify the first cytoplasmic role of Rap1 and provide a mechanism through which it regulates an important signalling cascade in mammals, independent of its ability to regulate telomere function."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.org/dc/terms/identifier"doi:10.1038/ncb2080"xsd:string
http://purl.uniprot.org/citations/20622870http://purl.org/dc/terms/identifier"doi:10.1038/ncb2080"xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Ghosh S."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Ghosh S."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Ghosh A."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Ghosh A."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Malik N."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Malik N."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Schultz P."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Schultz P."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Verma I.M."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Verma I.M."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Wong M."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Wong M."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Oliver J.D."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Oliver J.D."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Saez E."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Saez E."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Chanda S.K."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Chanda S.K."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Teo H."xsd:string
http://purl.uniprot.org/citations/20622870http://purl.uniprot.org/core/author"Teo H."xsd:string