Figure 1.

Oxygen-dependent regulation of HIFα and its target genes. HIFα is continuously hydroxylated by PHDs and FIH in sufficiently oxygenated environments (left). Hydroxylation of two proline residues by PHDs leads to subsequent proteasomal degradation after binding with VHL, whereas asparagine hydroxylation by FIH inhibits the interaction of HIF with p300/CBP and prevents transcriptional activation. Under hypoxia (right), HIFα is stabilized and translocates to the nucleus, binding to HIFβ as well as other co-factors, which promotes the transcriptional activation of target genes that harbor HRE sequences in their promoter region (HIF: hypoxia-inducible factor, FIH: factor inhibiting HIF, PHD: prolyl hydroxylase domain, VHL: von Hippel–Lindau, CBP: CREB-binding protein, HRE: hypoxia responsive element).