Abstract
The hypoxia-inducible factor (HIF) transcription complex, which is activated by low oxygen tension, controls a diverse range of cellular processes including angiogenesis and erythropoiesis. Under normoxic conditions, the alpha subunit of HIF is rapidly degraded in a manner dependent on hydroxylation of two conserved proline residues at positions 402 and 564 in HIF-1alpha in the oxygen-dependent degradation (ODD) domain. This allows subsequent recognition by the von Hippel-Lindau (VHL) tumor suppressor protein, which targets HIF for degradation by the ubiquitin-proteasome pathway. Under hypoxic conditions, prolyl hydroxylation of HIF is inhibited, allowing it to escape VHL-mediated degradation. The transcriptional regulation of the erythropoietin gene by HIF raises the possibility that HIF may play a role in disorders of erythropoiesis, such as idiopathic erythrocytosis (IE).
Original language | English |
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Pages (from-to) | 31-31 |
Number of pages | 1 |
Journal | Molecular Cancer Therapeutics |
Volume | 2 |
DOIs | |
Publication status | Published - 09 Sep 2003 |
Keywords
- Binding Sites
- DNA
- DNA Mutational Analysis
- Female
- Humans
- Hydroxylation
- Hypoxia-Inducible Factor 1, alpha Subunit
- Male
- Mutation, Missense
- Oxygen
- Polycythemia
- Polymorphism, Genetic
- Proline
- Transcription Factors