Signalling via the hypoxia-inducible factor-1alpha requires multiple posttranslational modifications

Cell Signal. 2005 Jan;17(1):1-9. doi: 10.1016/j.cellsig.2004.04.010.


Cellular hypoxia, a local decrease in the oxygen concentration below normal (21%) atmospheric concentrations, occurs in both physiological and pathological situations. The transcriptional complex Hypoxia-Inducible Factor-1 (HIF-1) is the key player in the signalling pathway that controls the hypoxic response of mammalian cells. Tight regulation of this response involves posttranslational modification of the alpha subunit of HIF-1. Hydroxylation, ubiquitination, acetylation, S-nitrosation and phosphorylation have been shown to determine its half-life and/or transcriptional activity. The precise spatio-temporal occurrence of these multiple modifications is still not fully understood but is dependent on the microenvironment and determines the driving force of variable cellular responses.

Publication types

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

MeSH terms

  • Animals
  • Cell Hypoxia / physiology*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • Signal Transduction / physiology*
  • Transcription Factors / metabolism*


  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transcription Factors