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| http://purl.uniprot.org/citations/15024078 | http://www.w3.org/2000/01/rdf-schema#comment | "The hypoxia-inducible factor 1 (HIF-1) transcriptional complex is regulated by cellular oxygen levels and growth factors. The phosphoinosotide 3-kinase (PI-3K)-Akt/protein kinase B (PKB) pathway has been shown to regulate HIF-1 activity in response to oncogenic signals and growth factors. We assessed whether the HDM2 oncoprotein, a direct target of Akt/PKB, could regulate HIF-1alpha expression and HIF-1 activity under normoxic conditions. We found that growth factor stimulation, overexpression of Akt/PKB, or loss of PTEN resulted in enhanced expression of both HIF-1alpha and HDM2. Growth factor-mediated induction of HIF-1alpha was ablated by transient expression of a dominant negative form of Akt/PKB or by treatment with LY294002. Transient expression of HDM2 led to increased expression of HIF-1alpha. Pulse-chase and cycloheximide experiments revealed that HDM2 did not significantly affect the half-life of HIF-1alpha. Growth factor-induced HIF-1alpha and HDM2 proteins were localized to the nucleus, and induction of both proteins was observed in both p53(+/+) and p53(-/-) HCT116 cells to comparable levels. Importantly, insulin-like growth factor 1-induced HIF-1alpha expression was observed in p53-null mouse embryo fibroblasts (MEFs) but was significantly impaired in p53 Mdm2 double-null MEFs, indicating a requirement for Mdm2 in this process. Finally, we showed that phosphorylation at Ser166 in HDM2 contributed in part to growth factor-mediated induction of HIF-1alpha. Our study has important implications for the role of the PI-3K-Akt/PKB-HDM2 pathway in tumor progression and angiogenesis."xsd:string |
| http://purl.uniprot.org/citations/15024078 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.24.7.2905-2914.2004"xsd:string |
| http://purl.uniprot.org/citations/15024078 | http://purl.uniprot.org/core/author | "Bardos J.I."xsd:string |
| http://purl.uniprot.org/citations/15024078 | http://purl.uniprot.org/core/author | "Ashcroft M."xsd:string |
| http://purl.uniprot.org/citations/15024078 | http://purl.uniprot.org/core/author | "Chau N.M."xsd:string |
| http://purl.uniprot.org/citations/15024078 | http://purl.uniprot.org/core/date | "2004"xsd:gYear |
| http://purl.uniprot.org/citations/15024078 | http://purl.uniprot.org/core/name | "Mol Cell Biol"xsd:string |
| http://purl.uniprot.org/citations/15024078 | http://purl.uniprot.org/core/pages | "2905-2914"xsd:string |
| http://purl.uniprot.org/citations/15024078 | http://purl.uniprot.org/core/title | "Growth factor-mediated induction of HDM2 positively regulates hypoxia-inducible factor 1alpha expression."xsd:string |
| http://purl.uniprot.org/citations/15024078 | http://purl.uniprot.org/core/volume | "24"xsd:string |
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