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. 2001 Apr 20;292(5516):464-8.
doi: 10.1126/science.1059817. Epub 2001 Apr 5.

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

M Ivan  1 , K Kondo, H Yang, W Kim, J Valiando, M Ohh, A Salic, J M Asara, W S Lane, W G Kaelin Jr
Affiliations

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

M Ivan et al. Science. .

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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