Factor inhibiting hypoxia-inducible factor (FIH)

Factor inhibiting hypoxia-inducible factor (FIH) is a 2-oxoglutarate and Fe(II)-dependent dioxygenase enzyme that catalyzes the hydroxylation of a conserved asparagine residue within the C-terminal transactivation domain of HIF-α proteins, restricting their ability to interact with transcriptional coactivators and thereby repressing HIF-mediated transcriptional activity under normal oxygen conditions (normoxia). FIH acts as a cellular oxygen sensor and regulates transcriptional responses to hypoxia. Apart from HIF-α, FIH also modifies proteins containing ankyrin repeat domains, though the biological significance of these modifications remains partly unresolved. Due to its central role in oxygen-dependent gene regulation, FIH is being explored as a drug target in diseases such as cancer and ischemia, where hypoxia and metabolic regulation are critical.

Other names

FIHFIH-1Factor-inhibiting HIF-1Asparaginyl hydroxylase

Inhibition of FIH enzymatic activity (asparaginyl hydroxylase), resulting in reduced hydroxylation of HIF-α, enhanced HIF-α transcriptional activity, and upregulated cellular hypoxic response Modulation of oxygen sensing and adaptation via alteration of HIF target gene expression