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

      Science (New York, N.Y.)
      American Association for the Advancement of Science (AAAS)

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          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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          Journal
          11292862
          10.1126/science.1059817

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