The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing

Biochem Biophys Res Commun. 2005 Dec 9;338(1):627-38. doi: 10.1016/j.bbrc.2005.08.165. Epub 2005 Aug 30.


The heterodimeric transcription factor HIF (hypoxia-inducible factor), consisting of a labile alpha-subunit and a stable beta-subunit, is a master regulator of genes involved in acute or chronic adaptation to low oxygen. Studies performed over the past 5 years revealed that HIFalpha-subunits are enzymatically hydroxylated in an oxygen-dependent manner. Hydroxylation of either of two conserved prolyl residues targets HIFalpha for destruction by a ubiquitin ligase containing the von Hippel-Lindau tumor suppressor protein whereas hydroxylation on a C-terminal asparagine affects HIF transactivation function. Pharmacological manipulation of HIF activity might be beneficial in diseases characterized by abnormal tissue oxygenation including myocardial infarction, cerebrovascular disease, and cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Hydroxylation
  • Hypoxia-Inducible Factor 1 / agonists
  • Hypoxia-Inducible Factor 1 / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1 / metabolism*
  • Oxygen / chemistry
  • Oxygen / metabolism*
  • Von Hippel-Lindau Tumor Suppressor Protein / chemistry
  • Von Hippel-Lindau Tumor Suppressor Protein / genetics
  • Von Hippel-Lindau Tumor Suppressor Protein / physiology*
  • von Hippel-Lindau Disease / genetics
  • von Hippel-Lindau Disease / metabolism


  • Hypoxia-Inducible Factor 1
  • Von Hippel-Lindau Tumor Suppressor Protein
  • Oxygen