In normoxic conditions, HIF-α subunits are hydroxylated by prolyl hydroxylase domain (PHD) enzymes, which mark them for proteasomal degradation via the von Hippel-Lindau (VHL) ubiquitin ligase complex. Under hypoxic conditions, the activity of PHD enzymes is inhibited, allowing HIF-α to stabilize, translocate to the nucleus, dimerize with HIF-β, and activate the transcription of target genes.
