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.

Keywords

HydroxylationUbiquitin ligaseProlineUbiquitinChemistryPeptideTranscription factorUbiquitin-Protein LigasesHypoxia-inducible factorsBiochemistrySuppressorCell biologyBiologyAmino acidEnzymeGene

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Publication Info

Year
2001
Type
article
Volume
292
Issue
5516
Pages
464-468
Citations
4615
Access
Closed

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Mircea Ivan, Keiichi Kondo, Haifeng Yang et al. (2001). HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O <sub>2</sub> Sensing. Science , 292 (5516) , 464-468. https://doi.org/10.1126/science.1059817

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DOI
10.1126/science.1059817