Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression

FASEB J. 2002 Aug;16(10):1151-62. doi: 10.1096/fj.01-0944rev.

Abstract

Although it was known for a long time that oxygen deprivation leads to the transcriptional induction of the gene encoding erythropoietin, the molecular mechanisms behind this process remained enigmatic. The cloning of the hypoxia-inducible factors (HIFs), the finding that HIF-1 regulates the expression of many more genes apart from erythropoietin, and the elucidation of the oxygen-dependent mechanisms degrading the HIF alpha subunits recently led to the spectacular discovery of the molecular principles of oxygen sensing. This review aims to summarize our current knowledge of oxygen-regulated gene expression..

Publication types

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

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Cell Hypoxia
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Glucose / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Iron / metabolism
  • Ligases / metabolism
  • Mixed Function Oxygenases / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / physiology
  • Oxygen / metabolism*
  • Oxygen / physiology*
  • Receptors, Aryl Hydrocarbon*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology
  • Transcriptional Activation
  • Tumor Suppressor Proteins*
  • Ubiquitin-Protein Ligases*
  • Von Hippel-Lindau Tumor Suppressor Protein

Substances

  • ARNT protein, human
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Receptors, Aryl Hydrocarbon
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Iron
  • Mixed Function Oxygenases
  • Ubiquitin-Protein Ligases
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Ligases
  • VHL protein, human
  • Glucose
  • Oxygen