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

Abstract

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.

• Authors: William G Kaelin Jr
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 338 Issue 1 Pg. 627-38 (Dec 09 2005) ISSN: 0006-291X [Print] United States
• PMID: 16153592 (Publication Type: Journal Article, Review)

Chemical References

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

Topics

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