From erythropoietin to oxygen: hypoxia-inducible factor hydroxylases and the hypoxia signal pathway

Blood Purif. 2002;20(5):445-50. doi: 10.1159/000065201.

Abstract

The regulation of blood red cell production by the hormone erythropoietin (Epo) provides a paradigm for control of gene expression by oxygen. Analysis of this pathway has revealed a widespread system of gene regulation based on a transcriptional complex termed hypoxia-inducible factor (HIF). Hydroxylation of specific prolyl and asparinyl residues in the alpha subunit of HIF by a series of non-haem iron-dependent dioxygenases has been defined as a novel mechanism of protein modification that transduces the oxygen-sensitive signal.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA-Binding Proteins / metabolism
  • Erythropoietin / physiology*
  • Gene Expression Regulation
  • Humans
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Ligases / metabolism
  • Mixed Function Oxygenases
  • Nuclear Proteins / metabolism
  • Oxygen / physiology*
  • Procollagen-Proline Dioxygenase / metabolism
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Von Hippel-Lindau Tumor Suppressor Protein

Substances

  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Repressor Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Erythropoietin
  • Mixed Function Oxygenases
  • HIF1AN protein, human
  • Procollagen-Proline Dioxygenase
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human
  • Oxygen