A common polymorphism in the oxygen-dependent degradation (ODD) domain of hypoxia inducible factor-1alpha (HIF-1alpha) does not impair Pro-564 hydroxylation

Melanie J Percy, Sharon M Mooney, Mary Frances McMullin, Adrian Flores, Terence R J Lappin, Frank S Lee

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

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 languageEnglish
Pages (from-to)31-31
Number of pages1
JournalMolecular Cancer Therapeutics
Volume2
DOIs
Publication statusPublished - 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

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