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http://purl.uniprot.org/citations/12615973http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12615973http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12615973http://www.w3.org/2000/01/rdf-schema#comment"Hypoxia-inducible factor1 (HIF-1) is an essential transcription factor for cellular adaptation to decreased oxygen availability. In normoxia the oxygen-sensitive alpha-subunit of HIF-1 is hydroxylated on Pro564 and Pro402 and thus targeted for proteasomal degradation. Three human oxygen-dependent HIF-1 alpha prolyl hydroxylases (PHD1, PHD2, and PHD3) function as oxygen sensors in vivo. Furthermore, the asparagine hydroxylase FIH-1 (factor inhibiting HIF) has been found to hydroxylate Asp803 of the HIF-1 C-terminal transactivation domain, which results in the decreased ability of HIF-1 to bind to the transcriptional coactivator p300/CBP. We have fused these enzymes to the N-terminus of fluorescent proteins and transiently transfected the fusion proteins into human osteosarcoma cells (U2OS). Three-dimensional 2-photon confocal fluorescence microscopy showed that PHD1 was exclusively present in the nucleus, PHD2 and FIH-1 were mainly located in the cytoplasm and PHD3 was homogeneously distributed in cytoplasm and nucleus. Hypoxia did not influence the localisation of any enzyme under investigation. In contrast to FIH-1, each PHD inhibited nuclear HIF-1 alpha accumulation in hypoxia. All hydroxylases suppressed activation of a cotransfected hypoxia-responsive luciferase reporter gene. Endogenous PHD2mRNA and PHD3mRNA were hypoxia-inducible, whereas expression of PHD1mRNA and FIH-1mRNA was oxygen independent. We propose that PHDs and FIH-1 form an oxygen sensor cascade of distinct subcellular localisation."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.org/dc/terms/identifier"doi:10.1242/jcs.00318"xsd:string
http://purl.uniprot.org/citations/12615973http://purl.org/dc/terms/identifier"doi:10.1242/jcs.00318"xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Jelkmann W."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Jelkmann W."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Klinger M."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Klinger M."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Stengel P."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Stengel P."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Acker H."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Acker H."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Berchner-Pfannschmidt U."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Berchner-Pfannschmidt U."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Fandrey J."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Fandrey J."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Hellwig-Burgel T."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Hellwig-Burgel T."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Huang W.Q."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Huang W.Q."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Marxsen J.H."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Marxsen J.H."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Metzen E."xsd:string
http://purl.uniprot.org/citations/12615973http://purl.uniprot.org/core/author"Metzen E."xsd:string