Signalling hypoxia by HIF hydroxylases.
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.
Schofield
Christopher J
CJ
Oxford Centre for Molecular Sciences, Department of Chemistry, Mansfield Road, Oxford OX1 3TA, UK.
Ratcliffe
Peter J
PJ
D000818:Animals; D006801:Humans; D000860:Hypoxia / Q000201:enzymology* / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D051793:Hypoxia-Inducible Factor 1; D006899:Mixed Function Oxygenases