The transcription factor hypoxia inducible factora-subunit (HIFa)is pivotal in the cellular response to the stress of hypoxia. Post-translational modification of HIFa by hydroxylase enzymes has recently been identified as a key oxygen sensing mechanism within the cell. The absence of the substrate oxygen prevents the hydroxylases from modi-fying HIFaduring hypoxia and allows dramatic up-regula-tion of both HIFaprotein stability and transcriptional activation capability.