| http://purl.uniprot.org/citations/17965024 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17965024 | http://www.w3.org/2000/01/rdf-schema#comment | "Oxygen homeostasis represents an essential organizing principle of metazoan evolution and biology. Hypoxia-inducible factor 1 (HIF-1) is a master regulator of transcriptional responses to changes in O2 concentration. HIF-1 is a heterodimer of HIF-1alpha and HIF-1beta subunits. O2-dependent degradation of the HIF-1alpha subunit is mediated by prolyl hydroxylase, von Hippel-Lindau protein (VHL)/Elongin-C E3 ubiquitin ligase, and the proteasome. O2-independent degradation of HIF-1alpha is regulated by the competition of RACK1 and HSP90 for binding to HIF-1alpha. RACK1 binding results in the recruitment of the Elongin-C E3 ubiquitin ligase, leading to VHL-independent ubiquitination and degradation of HIF-1alpha. In this report, we show that calcineurin inhibits the ubiquitination and proteasomal degradation of HIF-1alpha. Calcineurin is a serine/threonine phosphatase that is activated by calcium and calmodulin. The phosphatase activity of calcineurin is required for its regulation of HIF-1alpha. RACK1 binds to the catalytic domain of calcineurin and is required for HIF-1alpha degradation induced by the calcineurin inhibitor cyclosporine A. Elongin-C and HIF-1alpha each bind to RACK1 and dimerization of RACK1 is required to recruit Elongin-C to HIF-1alpha. Phosphorylation of RACK1 promotes its dimerization and dephosphorylation by calcineurin inhibits dimerization. Serine 146 within the dimerization domain is phosphorylated and mutation of serine 146 impairs RACK1 dimerization and HIF-1alpha degradation. These results indicate that intracellular calcium levels can regulate HIF-1alpha expression by modulating calcineurin activity and RACK1 dimerization."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m705015200"xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/author | "Cole R.N."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/author | "Liu J.O."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/author | "Pan F."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/author | "Semenza G.L."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/author | "Mansharamani M."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/author | "Liu Y.V."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/author | "McDonald K.R."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/author | "Hubbi M.E."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/pages | "37064-37073"xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/title | "Calcineurin promotes hypoxia-inducible factor 1alpha expression by dephosphorylating RACK1 and blocking RACK1 dimerization."xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://purl.uniprot.org/core/volume | "282"xsd:string |
| http://purl.uniprot.org/citations/17965024 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17965024 |
| http://purl.uniprot.org/citations/17965024 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/17965024 |
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| http://purl.uniprot.org/uniprot/#_B4E2K5-mappedCitation-17965024 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/17965024 |