| http://purl.uniprot.org/citations/15258597 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15258597 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15258597 | http://www.w3.org/2000/01/rdf-schema#comment | "NF-kappaB transcription factors mediate the effects of pro-inflammatory cytokines such as tumour necrosis factor-alpha and interleukin-1beta. Failure to downregulate NF-kappaB transcriptional activity results in chronic inflammation and cell death, as observed in A20-deficient mice. A20 is a potent inhibitor of NF-kappaB signalling, but its mechanism of action is unknown. Here we show that A20 downregulates NF-kappaB signalling through the cooperative activity of its two ubiquitin-editing domains. The amino-terminal domain of A20, which is a de-ubiquitinating (DUB) enzyme of the OTU (ovarian tumour) family, removes lysine-63 (K63)-linked ubiquitin chains from receptor interacting protein (RIP), an essential mediator of the proximal TNF receptor 1 (TNFR1) signalling complex. The carboxy-terminal domain of A20, composed of seven C2/C2 zinc fingers, then functions as a ubiquitin ligase by polyubiquitinating RIP with K48-linked ubiquitin chains, thereby targeting RIP for proteasomal degradation. Here we define a novel ubiquitin ligase domain and identify two sequential mechanisms by which A20 downregulates NF-kappaB signalling. We also provide an example of a protein containing separate ubiquitin ligase and DUB domains, both of which participate in mediating a distinct regulatory effect."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature02794"xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature02794"xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Aravind L."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Aravind L."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Koonin E.V."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Koonin E.V."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Zhou H."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Zhou H."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Seshagiri S."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Seshagiri S."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Boone D.L."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Boone D.L."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Dixit V.M."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Dixit V.M."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Wu P."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Wu P."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Baker R."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Baker R."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Ma A."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Ma A."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Wiesmann C."xsd:string |
| http://purl.uniprot.org/citations/15258597 | http://purl.uniprot.org/core/author | "Wiesmann C."xsd:string |