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Differential responses of two degradation domains of HIF-1alpha to hypoxia and iron deficiency

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dc.contributor.authorLee, Kyoung-Hwa-
dc.contributor.authorChoi, Eunjoo-
dc.contributor.authorChun, Yang-Sook-
dc.contributor.authorKim, Myung-Suk-
dc.contributor.authorPark, Jong-Wan-
dc.date.accessioned2010-01-04-
dc.date.available2010-01-04-
dc.date.issued2006-
dc.identifier.citationBiochimie 88 (2006) 163-169en
dc.identifier.issn0300-9084 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16139409-
dc.identifier.urihttps://hdl.handle.net/10371/24799-
dc.description.abstractHIF-1alpha is a transcription factor involved in the cellular adaptation to either hypoxia or iron deficiency. In the presence of oxygen and iron, proline residues in two degradation domains are modified by HIF-1-prolyl hydroxylases (PHDs), resulting in ubiquitination and degradation of HIF-1alpha. Since both molecular oxygen and iron are elements required for this hydroxylation process, HIF-1alpha might be unmodified and stable in conditions lacking oxygen or iron. If so, two degradation domains may respond to hypoxia and iron-depletion in the same way. In this study, however, we found two degradation domains to differentially regulate the stability of HIF-1alpha. The C-terminal domain responded to both hypoxia and iron-depletion, but the N-terminal domain to only iron-depletion. The deletion or point-mutation of the C-terminal domain blunted the hypoxic induction of HIF-1alpha. However, PHD-silencing siRNAs revealed that two degradation domains were not regulated by different types of PHDs. Both domains were regulated mainly by PHD2. The further mutational analysis demonstrated that the ARD1-acetylated motif near the C-terminal degradation domain (CDD) modulates the oxygen-dependent regulation of HIF-1alpha. The oxygen-dependent HIF-1alpha regulation requiring both proline hydroxylation and lysine acetylation may be more complicated than the iron-dependent regulation requiring only proline hydroxylation.en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectAnoxia/*metabolismen
dc.subjectCell Lineen
dc.subjectDeferoxamine/metabolismen
dc.subjectHumansen
dc.subjectHypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolismen
dc.subjectIron/*deficiency/metabolismen
dc.subjectOxygen/*metabolismen
dc.subjectPoint Mutationen
dc.subjectProtein Structure, Tertiaryen
dc.subjectRNA, Small Interfering/genetics/metabolismen
dc.subjectRNA, Small Interfering/genetics/metabolismen
dc.titleDifferential responses of two degradation domains of HIF-1alpha to hypoxia and iron deficiencyen
dc.typeArticleen
dc.contributor.AlternativeAuthor이경화-
dc.contributor.AlternativeAuthor최은주-
dc.contributor.AlternativeAuthor전양숙-
dc.contributor.AlternativeAuthor김명석-
dc.contributor.AlternativeAuthor박종완-
dc.identifier.doi10.1016/j.biochi.2005.07.011-
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