HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
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- 20 April 2001
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 292 (5516), 464-468
- https://doi.org/10.1126/science.1059817
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.Keywords
This publication has 28 references indexed in Scilit:
- The von Hippel–Lindau tumor suppressor proteinCurrent Opinion in Genetics & Development, 2001
- Inhibition of prolyl 4-hydroxylase in vitro and in vivo by members of a novel series of phenanthrolinonesBiochemical Journal, 2001
- Mechanism of regulation of the hypoxia-inducible factor-1alpha by the von Hippel-Lindau tumor suppressor proteinThe EMBO Journal, 2000
- Hypoxia Inducible Factor-α Binding and Ubiquitylation by the von Hippel-Lindau Tumor Suppressor ProteinPublished by Elsevier BV ,2000
- Control of β-Catenin StabilityMolecular Cell, 2000
- Regulation of Mammalian O2Homeostasis by Hypoxia-Inducible Factor 1Annual Review of Cell and Developmental Biology, 1999
- Characterization of an Oxygen/Redox-Dependent Degradation Domain of Hypoxia-Inducible Factor α (HIF-α) ProteinsBiochemical and Biophysical Research Communications, 1999
- Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitorHepatology, 1998
- Activation of Hypoxia-inducible Factor-1; Definition of Regulatory Domains within the α SubunitPublished by Elsevier BV ,1997
- The effect of hypoxia on collagen synthesis in cultured 3T6 fibroblasts and its relationship to the mode of action of ascorbateBiochimica et Biophysica Acta (BBA) - General Subjects, 1976