Hypoxia-inducible factor 1α protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations
| dc.creator | Sutter, Carrie Hayes | |
| dc.creator | Laughner, Erik | |
| dc.creator | Semenza, Gregg L. | |
| dc.date | 2000-04-11 | |
| dc.date.accessioned | 2026-08-02T19:47:19Z | |
| dc.description | 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-1α subunit. Under nonhypoxic conditions, HIF-1α protein is subject to ubiquitination and proteasomal degradation. Here we report that missense mutations and/or deletions involving several different regions of HIF-1α result in constitutive expression and transcriptional activity in nonhypoxic cells. We demonstrate that hypoxia results in decreased ubiquitination of HIF-1α and that missense mutations increase HIF-1α expression under nonhypoxic conditions by blocking ubiquitination. | |
| dc.identifier | https://pmc.ncbi.nlm.nih.gov/articles/PMC18304/ | |
| dc.identifier | https://pubmed.ncbi.nlm.nih.gov/10758161/ | |
| dc.identifier | https://doi.org/10.1073/pnas.080072497 | |
| dc.identifier.uri | https://repo.dare.co.zw/handle/123456789/78043 | |
| dc.language | en | |
| dc.publisher | National Academy of Sciences | |
| dc.rights | Copyright © The National Academy of Sciences | |
| dc.source | Proc Natl Acad Sci U S A | |
| dc.subject | Biological Sciences | |
| dc.title | Hypoxia-inducible factor 1α protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations | |
| dc.type | Text |