HIF1AN (FIH, FIH-1) forms a homodimer that hydroxylates an asparagine residue on HIF1A and HIF2A (Hewitson et al. 2002, Lando et al. 2002, Metzen et al. 2003, Lancaster et al. 2004). The hydroxylation of the asparagine interferes with the interaction between HIF1A/HIF2A and p300, a histone acetylase, and therefore inhibits the ability of HIF1A/2A to activate transcription of target genes (Lando et al. 2002). Because molecular oxygen is a substrate of the reaction, hypoxia is a negative regulator of this reaction and thereby increases transcriptional activation of target genes by HIF1A/2A.
|14701857||Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases||J Biol Chem||2004|
|15239670||Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity||Biochem J||2004|
|12080085||FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor||Genes Dev||2002|
|12042299||Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family||J Biol Chem||2002|
|11823643||Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch||Science||2002|