| http://purl.uniprot.org/citations/18621737 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18621737 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18621737 | http://www.w3.org/2000/01/rdf-schema#comment | "The inhibitor of apoptosis (IAP) proteins are a family of anti-apoptotic regulators found in viruses and metazoans. c-IAP1 and c-IAP2 are recruited to tumor necrosis factor receptor 1 (TNFR1)-associated complexes where they can regulate receptor-mediated signaling. Both c-IAP1 and c-IAP2 have been implicated in TNFalpha-stimulated NF-kappaB activation. However, individual c-IAP1 and c-IAP2 gene knock-outs in mice did not reveal changes in TNF signaling pathways, and the phenotype of a combined deficiency of c-IAPs has yet to be reported. Here we investigate the role of c-IAP1 and c-IAP2 in TNFalpha-stimulated activation of NF-kappaB. We demonstrate that TNFalpha-induced NF-kappaB activation is severely diminished in the absence of both c-IAP proteins. In addition, combined absence of c-IAP1 and c-IAP2 rendered cells sensitive to TNFalpha-induced cell death. Using cells with genetic ablation of c-IAP1 or cells where the c-IAP proteins were eliminated using IAP antagonists, we show that TNFalpha-induced RIP1 ubiquitination is abrogated in the absence of c-IAPs. Furthermore, we reconstitute the ubiquitination process with purified components in vitro and demonstrate that c-IAP1, in collaboration with the ubiquitin conjugating enzyme (E2) enzyme UbcH5a, mediates polymerization of Lys-63-linked chains on RIP1. Therefore, c-IAP1 and c-IAP2 are required for TNFalpha-stimulated RIP1 ubiquitination and NF-kappaB activation."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.c800128200"xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.c800128200"xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Fairbrother W.J."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Fairbrother W.J."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Vucic D."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Vucic D."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Deshayes K."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Deshayes K."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Dynek J.N."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Dynek J.N."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Fedorova A.V."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Fedorova A.V."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Goncharov T."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Goncharov T."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Varfolomeev E."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Varfolomeev E."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Zobel K."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/author | "Zobel K."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/18621737 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |