Factor inhibiting hypoxia-inducible factor 1 (FIH-1)

Factor inhibiting hypoxia-inducible factor 1 (FIH-1) is an asparaginyl hydroxylase enzyme that regulates the activity of hypoxia-inducible factor-1α (HIF-1α), a master transcription factor of the hypoxic response. FIH-1 hydroxylates HIF-1α at Asn-803 in the C-terminal transactivation domain under normoxic conditions, which prevents HIF-1α from recruiting transcriptional coactivators like p300/CBP, thus blocking hypoxia-responsive gene expression in the presence of oxygen[1][3][5][6]. FIH-1 is a non-heme Fe(II)/2-oxoglutarate–dependent dioxygenase and serves as a direct cellular oxygen sensor[1][3][6]. Modulating FIH-1 activity represents a potential strategy for treating ischemic disease and cancer by influencing cellular adaptation to hypoxia[5].

Other names

Factor-inhibiting HIF-1FIHHIF1NHIF asparaginyl hydroxylase

Inhibition of asparaginyl hydroxylase activity increases HIF transcriptional activation by blocking HIF-1α CTAD hydroxylation, allowing interaction with coactivators and expression of hypoxia response genes[1][3][5][6].