Fig. 7.

Regulation of HIF-2 under normoxic and hypoxic conditions. Under normoxic conditions, HIF-2α is hydroxylated by PHD2. Hydroxylated HIF-2α is then recognized by VHL, which then subsequently promotes ubiquitination of HIF-2α, ultimately leading to its degradation. In hypoxic conditions, the labile HIF-2α is stabilized by ROS and is allowed to interact with HIF-2β. HIF-2α/HIF-2β can then translocate to the nucleus and promote transcription of various hypoxia-signaling genes, promoting angiogenesis and erythropoiesis.

Abbreviations: HIF: hypoxia-inducible factor, PHD2: HIF prolyl hydroxylase domain-2, VHL: von Hippel-Lindau tumor-suppressor protein, ROS; reactive oxygen species, EndoMT: Endothelial-Mesenchymal Transition, TGF: transforming growth factor.