Figure 1
O2-dependent hydroxylation regulates HIF-1α ubiquitination and transactivation. The prolyl hydroxylase PHD2 binds to the oxygen-dependent degradation domain (ODD) of HIF-1α and, in the presence of O2, hydroxylates proline residue 402 and/or 564, which is required for the binding of VHL, which then recruits Elongin C and its associated E3 ubiquitin-protein ligase complex, which consists of Elongin B, RBX1, Cullin 2 (CUL2), and an E2 ubiquitin-conjugating enzyme. The hydroxylation by FIH-1 of asparagine-803 in the carboxyl-terminal transactivation domain of HIF-1α blocks coactivator (p300 or CBP) binding and HIF-1 transcriptional activity.
