| http://purl.uniprot.org/citations/17325032 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17325032 | http://www.w3.org/2000/01/rdf-schema#comment | "Hypoxia-inducible transcription factor 1alpha (HIF-1alpha) is a key player in the response to hypoxia. Additionally, HIF-1alpha responds to growth factors and hormones which can act via protein kinase B (Akt). However, HIF-1alpha is not a direct substrate for this kinase. Therefore, we investigated whether the protein kinase B target glycogen synthase kinase 3 (GSK-3) may have an impact on HIF-1alpha. We found that the inhibition or depletion of GSK-3 induced HIF-1alpha whereas the overexpression of GSK-3beta reduced HIF-1alpha. These effects were mediated via three amino acid residues in the oxygen-dependent degradation domain of HIF-1alpha. In addition, mutation analyses and experiments with von Hippel-Lindau (VHL)-defective cells indicated that GSK-3 mediates HIF-1alpha degradation in a VHL-independent manner. In line with these observations, the inhibition of the proteasome reversed the GSK-3 effects, indicating that GSK-3 may target HIF-1alpha to the proteasome by phosphorylation. Thus, the direct regulation of HIF-1alpha stability by GSK-3 may influence physiological processes or pathophysiological situations such as metabolic diseases or tumors."xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.00015-07"xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/author | "Kietzmann T."xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/author | "Michiels C."xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/author | "Gorlach A."xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/author | "Flugel D."xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/pages | "3253-3265"xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/title | "Glycogen synthase kinase 3 phosphorylates hypoxia-inducible factor 1alpha and mediates its destabilization in a VHL-independent manner."xsd:string |
| http://purl.uniprot.org/citations/17325032 | http://purl.uniprot.org/core/volume | "27"xsd:string |
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