HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing - PubMed (original) (raw)

. 2001 Apr 20;292(5516):464-8.

doi: 10.1126/science.1059817. Epub 2001 Apr 5.

Affiliations

• PMID: 11292862
• DOI: 10.1126/science.1059817

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

M Ivan et al. Science. 2001.

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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Comment in

• Signal transduction. How do cells sense oxygen?
  Zhu H, Bunn HF. Zhu H, et al. Science. 2001 Apr 20;292(5516):449-51. doi: 10.1126/science.1060849. Epub 2001 Apr 5. Science. 2001. PMID: 11292863 Free PMC article.
• Publish houses of brick, not mansions of straw.
  Kaelin WG Jr. Kaelin WG Jr. Nature. 2017 May 23;545(7655):387. doi: 10.1038/545387a. Nature. 2017. PMID: 28541345 No abstract available.

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