| http://purl.uniprot.org/citations/15221015 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15221015 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15221015 | http://www.w3.org/2000/01/rdf-schema#comment | "Smad7 negatively regulates transforming growth factor (TGF)-beta superfamily signaling by binding to activated type I receptors, thereby preventing the phosphorylation of receptor-regulated Smads (R-Smads), as well as by recruiting HECT-type E3 ubiquitin ligases to degrade type I receptors through a ubiquitin-dependent mechanism. To elucidate the regulatory mechanisms of TGF-beta signaling, we searched for novel members of proteins that interact with Smad7 using a yeast two-hybrid system. One of the proteins identified was the WW domain-containing protein 1 (WWP1) that is structurally related to Smad ubiquitin regulatory factors (Smurfs), E3 ubiquitin ligases for Smads and TGF-beta superfamily receptors. Using a TGF-beta-responsive reporter in mammalian cells, we found that WWP1 inhibited transcriptional activities induced by TGF-beta. Similar to Smurfs, WWP1 associated with Smad7 and induced its nuclear export, and enhanced binding of Smad7 to TGF-beta type I receptor to cause ubiquitination and degradation of the receptor. Consistent with these results, WWP1 inhibited phosphorylation of Smad2 induced by TGF-beta. WWP1 thus negatively regulates TGF-beta signaling in cooperation with Smad7. However, unlike Smurfs, WWP1 failed to ubiquitinate R-Smads and SnoN. Importantly, WWP1 and Smurfs were expressed in distinct patterns in human tissues and carcinoma cell lines, suggesting unique pathophysiological roles of WWP1 and Smurfs."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.org/dc/terms/identifier | "doi:10.1038/sj.onc.1207885"xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.org/dc/terms/identifier | "doi:10.1038/sj.onc.1207885"xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Yoshida Y."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Yoshida Y."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Imamura T."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Imamura T."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Miyazono K."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Miyazono K."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Saitoh M."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Saitoh M."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Miyazawa K."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Miyazawa K."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Komuro A."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Komuro A."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Yamori T."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/author | "Yamori T."xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/pages | "6914-6923"xsd:string |
| http://purl.uniprot.org/citations/15221015 | http://purl.uniprot.org/core/pages | "6914-6923"xsd:string |