FIG. 6.

Activation of HIF-1alpha by hypoxia. Under normoxic conditions, hypoxia-inducible factors are hydroxylated at conserved proline residues by prolyl hydroxylases. This leads to their recognition and ubiquitination by the VHL E3 ubiquitin ligase. In hypoxia, hydroxylation and degradation of HIFs do not occur, allowing them to dimerize with the HIF-1beta subunit, be transported into the nucleus, and execute their transcriptional function. HIF, hypoxia-inducible factor; VHL, Von Hippel–Lindau.