Factor inhibiting HIF-1 (FIH1) is an Fe (II)-dependent hydroxylase enzyme that serves as an oxygen sensor in the hypoxia response pathway (1). FIH1 binds to HIF-1alpha and inhibits its transactivation function. It also binds to VHL, which too functions as a transcriptional corepressor that inhibits HIF-1alpha transactivation function (2). In addition, FIH1 regulates the Notch signaling output and plays a role in how Notch signaling modulates the hypoxic response. It negatively regulates Notch activity and accelerates myogenic differentiation (3).
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