| http://purl.uniprot.org/citations/22286099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22286099 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22286099 | http://www.w3.org/2000/01/rdf-schema#comment | "There are three prolyl hydroxylases (PHD1, 2 and 3) that regulate the hypoxia-inducible factors (HIFs), the master transcriptional regulators that respond to changes in intracellular O(2) tension. In high O(2) tension (normoxia) the PHDs hydroxylate two conserved proline residues on HIF-1α, which leads to binding of the von Hippel-Lindau (VHL) tumour suppressor, the recognition component of a ubiquitin-ligase complex, initiating HIF-1α ubiquitylation and degradation. However, it is not known whether PHDs and VHL act separately to exert their enzymatic activities on HIF-1α or as a multiprotein complex. Here we show that the tumour suppressor protein LIMD1 (LIM domain-containing protein) acts as a molecular scaffold, simultaneously binding the PHDs and VHL, thereby assembling a PHD-LIMD1-VHL protein complex and creating an enzymatic niche that enables efficient degradation of HIF-1α. Depletion of endogenous LIMD1 increases HIF-1α levels and transcriptional activity in both normoxia and hypoxia. Conversely, LIMD1 expression downregulates HIF-1 transcriptional activity in a manner depending on PHD and 26S proteasome activities. LIMD1 family member proteins Ajuba and WTIP also bind to VHL and PHDs 1 and 3, indicating that these LIM domain-containing proteins represent a previously unrecognized group of hypoxic regulators."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.org/dc/terms/identifier | "doi:10.1038/ncb2424"xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.org/dc/terms/identifier | "doi:10.1038/ncb2424"xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Feng Y."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Feng Y."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Ratcliffe P.J."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Ratcliffe P.J."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Foxler D.E."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Foxler D.E."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "James V."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "James V."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Longmore G.D."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Longmore G.D."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Sharp T.V."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Sharp T.V."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Webb T.M."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Webb T.M."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Bjornsson J."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Bjornsson J."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Bridge K.S."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Bridge K.S."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Constantin-Teodosiu D."xsd:string |
| http://purl.uniprot.org/citations/22286099 | http://purl.uniprot.org/core/author | "Constantin-Teodosiu D."xsd:string |