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http://purl.uniprot.org/citations/20889502http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20889502http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20889502http://www.w3.org/2000/01/rdf-schema#comment"Polo-like kinase 3 (Plk3) plays an important role in the regulation of cell cycle progression and stress responses. Plk3 also has a tumor-suppressing activity as aging PLK3-null mice develop tumors in multiple organs. The growth of highly vascularized tumors in PLK3-null mice suggests a role for Plk3 in angiogenesis and cellular responses to hypoxia. By studying primary isogenic murine embryonic fibroblasts, we tested the hypothesis that Plk3 functions as a component in the hypoxia signaling pathway. PLK3(-/-) murine embryonic fibroblasts contained an enhanced level of HIF-1α under hypoxic conditions. Immunoprecipitation and pulldown analyses revealed that Plk3 physically interacted with HIF-1α under hypoxia. Purified recombinant Plk3, but not a kinase-defective mutant, phosphorylated HIF-1α in vitro, resulting in a major mobility shift. Mass spectrometry identified two unique serine residues that were phosphorylated by Plk3. Moreover, ectopic expression followed by cycloheximide or pulse-chase treatment demonstrated that phospho-mutants exhibited a much longer half-life than the wild-type counterpart, strongly suggesting that Plk3 directly regulates HIF-1α stability in vivo. Combined, our study identifies Plk3 as a new and essential player in the regulation of the hypoxia signaling pathway."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m110.160325"xsd:string
http://purl.uniprot.org/citations/20889502http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m110.160325"xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Lu L."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Lu L."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Xu D."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Xu D."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Yao Y."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Yao Y."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Dai W."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Dai W."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Costa M."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/author"Costa M."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/pages"38944-38950"xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/pages"38944-38950"xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/title"Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1alpha."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/title"Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1alpha."xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/volume"285"xsd:string
http://purl.uniprot.org/citations/20889502http://purl.uniprot.org/core/volume"285"xsd:string