Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators

Int J Biochem Cell Biol. 2005 Mar;37(3):535-40. doi: 10.1016/j.biocel.2004.08.012.


Oxygen availability is crucial for cellular metabolism. Hypoxia-inducible factor 1 (HIF-1) is the major oxygen homeostasis regulator. Under normoxic conditions, HIF-1 is rapidly degraded by the proteasome. However, under hypoxic conditions, HIF-1 is stabilized and permits the activation of genes essential to cellular adaptation to low oxygen conditions. These genes include the vascular endothelial growth factor (VEGF), erythropoietin and glucose transporter-1. There is increasing evidence showing that HIF-1 is also implicated in biological functions requiring its activation under normoxic conditions. Amongst others, growth factors and vascular hormones are implicated in this normoxic activation. In this review, we will focus on differences between hypoxic and non-hypoxic induction and activation of HIF-1. We will also discuss the biological functions of HIF-1 associated with these two induction pathways. The clear understanding of both HIF-1 activation mechanisms could have a major impact in cancer and vascular disease.

Publication types

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

MeSH terms

  • Animals
  • Cell Hypoxia
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Erythropoietin / genetics
  • Gene Expression Regulation*
  • Glucose Transporter Type 1
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Models, Biological
  • Monosaccharide Transport Proteins / genetics
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oxygen / physiology
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Structure, Tertiary
  • Trans-Activators / physiology*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation*
  • Vascular Endothelial Growth Factors / genetics


  • DNA-Binding Proteins
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Monosaccharide Transport Proteins
  • Nuclear Proteins
  • SLC2A1 protein, human
  • Trans-Activators
  • Transcription Factors
  • Vascular Endothelial Growth Factors
  • Erythropoietin
  • Proteasome Endopeptidase Complex
  • Oxygen