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    Science. 2001 Apr 20;292(5516):464-8. Epub 2001 Apr 5.

    HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.

    Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr.

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    Dana-Farber Cancer Institute and Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

    Abstract

    HIF (hypoxia-inducible factor) is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. In the presence of oxygen, HIF is targeted for destruction by an E3 ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein (pVHL). We found that human pVHL binds to a short HIF-derived peptide when a conserved proline residue at the core of this peptide is hydroxylated. Because proline hydroxylation requires molecular oxygen and Fe(2+), this protein modification may play a key role in mammalian oxygen sensing.

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    PMID:
    11292862
    [PubMed - indexed for MEDLINE]

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