Transduction pathways involved in Hypoxia-Inducible Factor-1 phosphorylation and activation

Free Radic Biol Med. 2001 Oct 1;31(7):847-55. doi: 10.1016/s0891-5849(01)00657-8.


Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor which is activated by hypoxia and involved in the adaptative response of the cell to oxygen deprivation. During hypoxic stress, HIF-1 triggers the overexpression of genes coding for glycolytic enzymes and angiogenic factors. To be active HIF-1 must be phosphorylated. HIF-1 is a substrate for various kinase pathways including PI-3K and the MAP kinases ERK and p38. Several transduction pathways have been proposed which act downstream of putative oxygen sensors and lead to the activation of these kinases. In this review, we summarize some of the latest advances describing the possible signaling pathways leading to HIF-1 phosphorylation and subsequent activation. The physiological relevance of these regulations is also discussed.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / genetics
  • Angiogenesis Inhibitors / metabolism
  • Animals
  • Cell Hypoxia / physiology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • DNA-Binding Proteins / pharmacology
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism*
  • Nuclear Proteins / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism
  • Transcription Factors / pharmacology
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics
  • Transcriptional Activation / physiology*
  • Transduction, Genetic


  • Angiogenesis Inhibitors
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • Transcription Factors
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases