In normoxic conditions, HIF1α is hydroxylated by PH, ubiquitinated by the VHL, and thus targeted to the proteasome for degradation. During hypoxia, PH-dependent hydroxylation is blocked and HIF1α stabilized, thus activating the hypoxic transcriptional response. PH, prolyl hydroxylase; VHL, von Hippel–Lindau factor; Ub, ubiquitin.