Figure 2.

Regulation of HIF-α protein by pVHL. In normoxia, two proline residues of HIF-α are hydroxylated by PHD1–3, and then HIF-α is recognized by pVHL for polyubiquitination and degradation by the proteasome. On the other hand, in hypoxia, HIF-α escapes prolyl hydroxylation and thereby escapes degradation. HIF-α then dimerizes with HIF-1β to form an active transcription complex. Prolonged activation of the HIFα/β transcription complex is a major contributor to VHL disease.