Expression of hypoxia-inducible factor 1: mechanisms and consequences

Biochem Pharmacol. 2000 Jan 1;59(1):47-53. doi: 10.1016/s0006-2952(99)00292-0.


Hypoxia-inducible factor 1 (HIF-1) is a basic-helix-loop-helix transcription factor that plays essential roles in mammalian development and physiology. HIF-1 is a heterodimer composed of HIF-1alpha and HIF-1beta subunits. The expression and activity of the HIF-1alpha subunit are tightly regulated by cellular O2 concentration. Under hypoxic conditions, HIF-1 activates the transcription of genes encoding erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other genes whose protein products increase O2 delivery or facilitate metabolic adaptation to hypoxia. HIF-1 is essential for embryonic vascularization and survival, neovascularization in ischemic myocardium, hypoxia-induced pulmonary vascular remodeling, and tumor vascularization. HIF-1alpha is overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors. Pharmacologic manipulation of HIF-1 levels may provide a novel therapeutic approach to diseases that represent the most common causes of mortality in Western society, including cancer, chronic lung disease, and myocardial ischemia.

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 / biosynthesis*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology
  • Homeostasis
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Neoplasms / metabolism
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / physiology
  • Oxygen / metabolism*
  • Protein Conformation
  • Signal Transduction
  • Transcription Factors*


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