Inhibition of the Oxygen-Sensing Asparaginyl Hydroxylase Factor Inhibiting Hypoxia-Inducible Factor: A Potential Hypoxia Response Modulating Strategy

Factor inhibiting hypoxia-inducible factor (FIH) is a JmjC domain 2-oxogluarate and Fe(II)-dependent oxygenase that catalyzes hydroxylation of specific asparagines in the C-terminal transcriptional activation alpha (HIF-?) isoforms. This modification suppresses activity HIF by reducing its interaction with coactivators p300/CBP. By contrast inhibition prolyl hydroxylases (PHDs), inhibitors FIH, which accepts multiple non-HIF substrates, are less studied; they interest due to their potential ability alter metabolism (either HIF-dependent and/or -independent manner) and, provided upregulated, modulate course HIF-mediated hypoxic response. Here we review studies on mechanism FIH. We discuss proposed biological roles FIH including regulation FIH-catalyzed oxidation substrates. highlight therapeutic applications inhibitors.