| http://purl.uniprot.org/citations/9859996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/9859996 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/9859996 | http://www.w3.org/2000/01/rdf-schema#comment | "NF-kappaB, a ubiquitous, inducible transcription factor involved in immune, inflammatory, stress and developmental processes, is retained in a latent form in the cytoplasm of non-stimulated cells by inhibitory molecules, IkappaBs. Its activation is a paradigm for a signal-transduction cascade that integrates an inducible kinase and the ubiquitin-proteasome system to eliminate inhibitory regulators. Here we isolate the pIkappaBalpha-ubiquitin ligase (pIkappaBalpha-E3) that attaches ubiquitin, a small protein which marks other proteins for degradation by the proteasome system, to the phosphorylated NF-kappaB inhibitor pIkappaBalpha. Taking advantage of its high affinity to pIkappaBalpha, we isolate this ligase from HeLa cells by single-step immunoaffinity purification. Using nanoelectrospray mass spectrometry, we identify the specific component of the ligase that recognizes the pIkappaBalpha degradation motif as an F-box/WD-domain protein belonging to a recently distinguished family of beta-TrCP/Slimb proteins. This component, which we denote E3RSIkappaB (pIkappaBalpha-E3 receptor subunit), binds specifically to pIkappaBalpha and promotes its in vitro ubiquitination in the presence of two other ubiquitin-system enzymes, E1 and UBC5C, one of many known E2 enzymes. An F-box-deletion mutant of E3RS(IkappaB), which tightly binds pIkappaBalpha but does not support its ubiquitination, acts in vivo as a dominant-negative molecule, inhibiting the degradation of pIkappaBalpha and consequently NF-kappaB activation. E3RS(IkappaB) represents a family of receptor proteins that are core components of a class of ubiquitin ligases. When these receptor components recognize their specific ligand, which is a conserved, phosphorylation-based sequence motif, they target regulatory proteins containing this motif for proteasomal degradation."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.org/dc/terms/identifier | "doi:10.1038/25159"xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.org/dc/terms/identifier | "doi:10.1038/25159"xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Andersen J.S."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Andersen J.S."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Mann M."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Mann M."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Davis M."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Davis M."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Amit S."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Amit S."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Manning A.M."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Manning A.M."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Yaron A."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Yaron A."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Ben-Neriah Y."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Ben-Neriah Y."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Hatzubai A."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Hatzubai A."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Lavon I."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Lavon I."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Mercurio F."xsd:string |
| http://purl.uniprot.org/citations/9859996 | http://purl.uniprot.org/core/author | "Mercurio F."xsd:string |