The hypoxia-inducible factor α subunits 1 and 2 (HIF-1α and HIF-2α) are subjected to
oxygen-dependent asparaginyl hydroxylation, a modification that represses the carboxyl-
terminal transactivation domain (CAD) at normoxia by preventing recruitment of the
p300/cAMP-response element-binding protein coactivators. This hydroxylation is performed
by the novel asparaginyl hydroxylase, factor-inhibiting HIF-1′(FIH-1), of which HIF-1α and
HIF-2α are the only reported substrates. Here we investigated the substrate requirements of …