Figure 1.

Schematic diagram of the HIF-1α pathway.

Notes: In normoxia (A), PHDs hydroxylate specific proline residues of HIF-1α, leading to its proteosomal degradation, mediated by pVHL, an E3 ubiquitin ligase. During hypoxia (B), the lack of oxygen inhibits the actions of PHDs, and HIF-1α is not ubiquitinylated and then degraded. HIF-1α builds up and translocates to the nucleus where it binds to HIF-1β and p300. This complex then acts as a transcription factor that binds to HREs to induce expression of hypoxia-regulated genes.

Abbreviations: UB, ubiquitin; HIF-1, hypoxia-inducible factor-1; OH, hydroxyl; VHL, von Hippel–Lindau protein; HRE, hypoxia response element; PHD, prolyl hydroxylase domain protein; p, phosphorylated.