Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations
- PMID: 10758161
- PMCID: PMC18304
- DOI: 10.1073/pnas.080072497
Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations
Erratum in
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Correction for Sutter et al., Hypoxia-inducible factor 1α protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations.Proc Natl Acad Sci U S A. 2022 Sep 20;119(38):e2210922119. doi: 10.1073/pnas.2210922119. Epub 2022 Sep 2. Proc Natl Acad Sci U S A. 2022. PMID: 36053737 Free PMC article. No abstract available.
Abstract
Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses to reduced O(2) availability in mammals, including angiogenesis, erythropoiesis, and glycolysis. HIF-1 activity is controlled by the O(2)-regulated expression of the HIF-1alpha subunit. Under nonhypoxic conditions, HIF-1alpha protein is subject to ubiquitination and proteasomal degradation. Here we report that missense mutations and/or deletions involving several different regions of HIF-1alpha result in constitutive expression and transcriptional activity in nonhypoxic cells. We demonstrate that hypoxia results in decreased ubiquitination of HIF-1alpha and that missense mutations increase HIF-1alpha expression under nonhypoxic conditions by blocking ubiquitination.
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