Figure 1.

Regulation of hypoxia-inducible factors. In normoxia, certain proline residues of the α subunits of the hypoxia-inducible factor (HIF) are hydroxylated by prolyl hydroxylases (PHDs) using oxygen. The hydroxyprolines (HP) allow von-Hippel-Lindau (VHL) protein to bind and ubiquitinate HIF-α, which results in their proteaosomal degradation. In contrast, HIF-α escapes from post-translational modification by PHDs in hypoxia. HIF-α forms a heterodimer with a β subunit (HIF-β) and then binds to a hypoxia response element (HRE) in the regulatory region of a target gene and promotes its transcription. Ub, ubiquitin.