HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing

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

Research output: Contribution to journalArticle

3402 Scopus citations

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 Fe2+, this protein modification may play a key role in mammalian oxygen sensing.

Original languageEnglish (US)
Pages (from-to)464-468
Number of pages5
JournalScience
Volume292
Issue number5516
DOIs
StatePublished - Apr 20 2001
Externally publishedYes

ASJC Scopus subject areas

  • General

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    Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin, J. (2001). HIFα targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science, 292(5516), 464-468. https://doi.org/10.1126/science.1059817