Asparagine-803 in the C-terminal transactivation domain of human hypoxia-inducible factor (HIF)-1 alpha-subunit is hydroxylated by factor inhibiting HIF-1 (FIH-1) under normoxic conditions causing abrogation of the HIF-1alpha/p300 interaction. NMR and other analyses of a hydroxylated HIF fragment produced in vitro demonstrate that hydroxylation occurs at the beta-carbon of Asn-803 and imply production of the threo-isomer, in contrast with other known aspartic acid/asparagine hydroxylases that produce the erythro-isomer.
- asparagine hydroxylation
- factor inhibiting hypoxia-inducible factor-1 (FIH-1)
- oxygen sensing