Turn me on: regulating HIF transcriptional activity

Cell Death Differ. 2008 Apr;15(4):642-9. doi: 10.1038/sj.cdd.4402315. Epub 2008 Jan 18.


The hypoxia-inducible factors (HIFs) are critical for cellular adaptation to limiting oxygen and regulate a wide array of genes when cued by cellular oxygen-sensing mechanisms. HIF is able to direct transcription from either of two transactivation domains, each of which is regulated by distinct mechanisms. The oxygen-dependent asparaginyl hydroxylase factor-inhibiting HIF-1alpha (FIH-1) is a key regulator of the HIF C-terminal transactivation domain, and provides a direct link between oxygen sensation and HIF-mediated transcription. Additionally, there are phosphorylation and nitrosylation events reported to modulate HIF transcriptional activity, as well as numerous transcriptional coactivators and other interacting proteins that together provide cell and tissue specificity of HIF target gene regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Hypoxia / genetics
  • DNA / metabolism
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Mixed Function Oxygenases
  • Oxygen / metabolism
  • Protein Conformation
  • Protein Structure, Tertiary
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transcriptional Activation*


  • Basic Helix-Loop-Helix Transcription Factors
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Repressor Proteins
  • Transcription Factors
  • endothelial PAS domain-containing protein 1
  • DNA
  • Mixed Function Oxygenases
  • HIF1AN protein, human
  • Oxygen