| http://purl.uniprot.org/citations/15496141 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15496141 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15496141 | http://www.w3.org/2000/01/rdf-schema#comment | "Inhibitory Smad, Smad7, is a potent inhibitor of TGF-beta (transforming growth factor-beta) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads). To identify new components of the Smad pathway, we performed yeast two-hybrid screening using Smad7 as bait, and identified NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) as a direct binding partner of Smad7. NEDD4-2 is structurally similar to Smurfs (Smad ubiquitin regulatory factors) 1 and 2, which were identified previously as E3 ubiquitin ligases for R-Smads and TGF-beta superfamily receptors. NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-beta type I receptor via Smad7, and induces its ubiquitin-dependent degradation. Moreover, NEDD4-2 bound to TGF-beta-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), although NEDD4-2 bound to SnoN via Smad2 more strongly than Smurf2. We showed further that overexpressed NEDD4-2 prevents transcriptional activity induced by TGF-beta and BMP, whereas silencing of the NEDD4-2 gene by siRNA (small interfering RNA) resulted in enhancement of the responsiveness to TGF-beta superfamily cytokines. These data suggest that NEDD4-2 is a member of the Smurf-like C2-WW-HECT (WW is Trp-Trp and HECT is homologous to the E6-accessory protein) type E3 ubiquitin ligases, which negatively regulate TGF-beta superfamily signalling through similar, but not identical, mechanisms to those used by Smurfs."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.org/dc/terms/identifier | "doi:10.1042/bj20040738"xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.org/dc/terms/identifier | "doi:10.1042/bj20040738"xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Goto K."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Goto K."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Imamura T."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Imamura T."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Miyazono K."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Miyazono K."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Miyazawa K."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Miyazawa K."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Shinozaki M."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Shinozaki M."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Komuro A."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Komuro A."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Kuratomi G."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/author | "Kuratomi G."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/name | "Biochem. J."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/name | "Biochem. J."xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/pages | "461-470"xsd:string |
| http://purl.uniprot.org/citations/15496141 | http://purl.uniprot.org/core/pages | "461-470"xsd:string |