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Biochem Biophys Res Commun. 2005 Dec 9;338(1):617-26. Epub 2005 Aug 24.

Signalling hypoxia by HIF hydroxylases.

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1
Oxford Centre for Molecular Sciences, Department of Chemistry, Mansfield Road, Oxford OX1 3TA, UK.

Abstract

Analysis of oxygen sensitive pathways that regulate the hypoxia inducible factor (HIF) transcriptional system has revealed a novel role for oxygenases in signalling hypoxia. The enzymes, which catalyse hydroxylation of specific prolyl and asparaginyl residues in the regulatory HIF-alpha subunits, belong to the superfamily of non-haem Fe(II)-dependent oxygenases that use the citric acid cycle intermediate 2-oxoglutarate (2OG) as a co-substrate. We review biochemical and physiological data that demonstrate a central role for these oxygenases in integrating multiple signals that coordinate cellular responses to hypoxia.

PMID:
16139242
DOI:
10.1016/j.bbrc.2005.08.111
[Indexed for MEDLINE]
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