Fig. 1

HIF regulation by PHD and FIH-1. Under normoxic conditions, PHDs hydroxylate specific proline residues on HIF-α, which allows it to be recognized by pVHL, to be polyubiquitinated and degraded in the proteasome. In contrast, under hypoxia, HIF-α escapes PHD-mediated hydroxylation, translocates to the nucleus, and forms a heterodimer with HIF-β. HIF heterodimers bind to hypoxia response elements in the regulatory regions of target genes, resulting in transactivation of these genes. In addition, FIH-1, an asparaginyl hydroxylase, hydroxylates one specific asparagine residue of HIF-1α. This modification inhibits the binding of coactivators p300 and CBP, resulting in repressed transactivation. PHD prolyl hydroxylase domain-containing protein, HIF hypoxia-inducible factor, pVHL von Hippel–Lindau tumor suppressor protein, FIH-1 factor inhibiting HIF-1, CBP CREB-binding protein