Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1

Annu Rev Cell Dev Biol. 1999;15:551-78. doi: 10.1146/annurev.cellbio.15.1.551.


Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic-helix-loop-helix-PAS transcription factor consisting of HIF-1 alpha and HIF-1 beta subunits. HIF-1 alpha expression and HIF-1 transcriptional activity increase exponentially as cellular O2 concentration is decreased. Several dozen target genes that are transactivated by HIF-1 have been identified, including those encoding erythropoietin, glucose transporters, glycolytic enzymes, and vascular endothelial growth factor. The products of these genes either increase O2 delivery or allow metabolic adaptation to reduced O2 availability. HIF-1 is required for cardiac and vascular development and embryonic survival. In fetal and postnatal life, HIF-1 is required for a variety of physiological responses to chronic hypoxia. HIF-1 expression is increased in tumor cells by multiple mechanisms and may mediate adaptation to hypoxia that is critical for tumor progression. HIF-1 thus appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology.

Publication types

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

MeSH terms

  • Animals
  • Cell Hypoxia
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / physiology
  • Forecasting
  • Helix-Loop-Helix Motifs*
  • Homeostasis
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mammals
  • Neoplasms / metabolism
  • Neoplasms / physiopathology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / physiology
  • Oxygen / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology


  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Transcription Factors
  • Oxygen