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PMID:10758161
| Citation |
Sutter, CH, Laughner, E and Semenza, GL (2000) Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations. Proc. Natl. Acad. Sci. U.S.A. 97:4748-53 |
|---|---|
| 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. |
| Links |
PubMed PMC18304 Online version:10.1073/pnas.080072497 |
| Keywords |
Cell Line; Cell Nucleus/metabolism; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Helix-Loop-Helix Motifs; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Macromolecular Substances; Mutagenesis, Site-Directed; Mutation, Missense; Nuclear Proteins/chemistry; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Oxygen/physiology; Point Mutation; Protein Processing, Post-Translational; Recombinant Proteins/chemistry; Recombinant Proteins/metabolism; Sequence Deletion; Transcription Factors/genetics; Transfection; Ubiquitins/metabolism |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0071456 : cellular response to hypoxia |
ECO:0000270: |
P |
Figure 1 |
complete | ||||
See also
References
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