Figure 1.

Under normoxic conditions, the proline and lysine residues on the oxygen-dependent degradation domain of HIF-1α are hydroxylated, and modified HIF-1α interacts with the Von Hippel-Lindau E3 ubiquitin ligase complex via ubiquitin-proteasome pathway degradation. However, HIF-1α is stable under hypoxic conditions. With the help of co-activators, such as CBP and p300, HIF-1α forms a heterodimer with HIF-1β, and then HIF-1α is transferred to the nucleus and combines with the target gene HRE to induce downstream gene expression. HIF, hypoxia-inducible factor; HRE, hypoxia response element; CBP, cyclic adenosine monophosphate response element binding protein; p300, acetyltransferase; VEGF, vascular endothelial growth factor; EPO, erythropoietin; GLUT, glucose transporter type.