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- Title
HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.
- Authors
Ivan, M; Kondo, K; Yang, H; Kim, W; Valiando, J; Ohh, M; Salic, A; Asara, J M; Lane, W S; Kaelin, W G, Jr
- 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.
- Publication
Science (New York, N.Y.), 2001, Vol 292, Issue 5516, p464
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.1059817