Fig. 1

Schematic diagram of oxygen-dependent HIF regulation. In normoxia, HIF-α subunits are hydroxylated on two conserved proline residues by ELGN1, ELGN2, or EGLN3. Hydroxylation of HIF-α subunit leads to rapid degradation through von Hippel-Lindau tumor suppressor protein (VHL) binding and proteasome-mediated degradation. In hypoxia, proline hydroxylation is inhibited resulting in decreased VHL binding and stabilization of protein. Following stabilization, HIF-α subunit forms a heterodimer with (ARNT) leading to activation of HIF target genes. ARNT aryl hydrocarbon receptor nuclear translocator, EGLN EGL nine homolog, HIF hypoxia-inducible factor, VHL von Hippel-Lindau tumor suppressor protein