Hypoxic response elements HREs

Figure 1 Role of prolyl hydroxylases as an oxygen-sensor regulating HIF activation. In the presence of oxygen, PHD enzymes convert specific prolyl residues in HIF-a chains to hydroxyproline. The enzymes require iron as a cofactor. Modified HIF-a chains are captured hy the pVHL ubiquitin E3 ligase complex, ubiquitylated, and destroyed by the proteasome. Under reduced oxygenation, HIF-a rapidly accumulates, enters the nucleus, dimerizes with a jS subunit, recruits coactivators, and activates transcription of genes with hypoxic response elements (HRE). HYP, hydroxyproline.

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