| http://purl.uniprot.org/citations/20699359 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20699359 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/20699359 | http://www.w3.org/2000/01/rdf-schema#comment | "Hypoxia-inducible factor 1 (HIF-1), a transcriptional activator that mediates cellular response to hypoxia and a promising target of anticancer therapy, is essential for adaptation to low oxygen conditions, embryogenesis and tumor progression. HIF-1 is a heterodimer of HIF-1alpha, expression of which is controlled by oxygen levels as well as by various oxygen-independent mechanisms, and HIF-1beta (or ARNT), which is constitutively expressed. In this work, we investigate the phosphorylation of the N-terminal heterodimerization (PAS) domain of HIF-1alpha and identify Ser247 as a major site of in vitro modification by casein kinase 1delta (CK1delta). Mutation of this site to alanine, surprisingly, enhanced the transcriptional activity of HIF-1alpha, a result phenocopied by inhibition or small interfering RNA (siRNA)-mediated silencing of CK1delta under hypoxic conditions. Conversely, overexpression of CK1delta or phosphomimetic mutation of Ser247 to aspartate inhibited HIF-1alpha activity without affecting its stability or nuclear accumulation. Immunoprecipitation and in vitro binding experiments suggest that CK1-dependent phosphorylation of HIF-1alpha at Ser247 impairs its association with ARNT, a notion also supported by modeling the structure of the complex between HIF-1alpha and ARNT PAS-B domains. We suggest that modification of HIF-1alpha by CK1 represents a novel mechanism that controls the activity of HIF-1 during hypoxia by regulating the interaction between its two subunits."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.org/dc/terms/identifier | "doi:10.1242/jcs.068122"xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.org/dc/terms/identifier | "doi:10.1242/jcs.068122"xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Simos G."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Simos G."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Chachami G."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Chachami G."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Kalousi A."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Kalousi A."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Mylonis I."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Mylonis I."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Paraskeva E."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Paraskeva E."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Politou A.S."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/author | "Politou A.S."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/name | "J. Cell Sci."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/name | "J. Cell Sci."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/pages | "2976-2986"xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/pages | "2976-2986"xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/title | "Casein kinase 1 regulates human hypoxia-inducible factor HIF-1."xsd:string |
| http://purl.uniprot.org/citations/20699359 | http://purl.uniprot.org/core/title | "Casein kinase 1 regulates human hypoxia-inducible factor HIF-1."xsd:string |