Figure 1.

The regulation of the HIFα by pVHL-containing E3 ubiquitin ligase complex. During normoxia, HIFα is produced and prolyl hydroxylated by PHD1–3. The hydroxyproline provides a binding signal for pVHL, which leads to efficient ubiquitylation and proteasomal degradation of HIFα protein. During hypoxia, HIFα is not prolyl hydroxylated and escapes pVHL recognition. HIFα accumulates and forms complex with HIF1β, goes into nucleus and turns on a transcriptional program to cope with the short-term and long-term effects of oxygen deprivation.