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Review

Nature Reviews Molecular Cell Biology 5, 343–354 (1 May 2004) | doi:10.1038/nrm1366

Oxygen sensing by HIF hydroxylases

Christopher J. Schofield & Peter J. Ratcliffe

The transcription factor HIF (hypoxia-inducible factor) has a central role in oxygen homeostasis in animals ranging from nematode worms to man. Recent studies have shown that this factor is regulated by an unprecedented signalling mechanism that involves post-translational hydroxylation. This hydroxylation is catalysed by a set of non-haem, Fe2+-dependent enzymes that belong to the 2-oxoglutarate-dependent-oxygenase superfamily. The absolute requirement of these enzymes for molecular oxygen has provided new insights into the way cells sense oxygen.