Cell growth and viability is compromised by oxygen deprivation (hypoxia). Hypoxia-inducible factors, including HIF-1α, HIF-1β (also designated Arnt 1), EPAS-1 (also designated HIF-2α) and HIF-3α, induce glycolysis, erythropoiesis and angiogenesis in order to restore oxygen homeostasis. Hypoxia-inducible factors are members of the Per-Arnt-Sim (PAS) domain transcription factor family. In response to hypoxia, HIF-1α is upregulated and forms a heterodimer with Arnt 1 to form the HIF-1 complex. The HIF-1 complex recognizes and binds to the hypoxia responsive element (HRE) of hypoxia-inducible genes, thereby activating transcription. Hypoxia-inducible expression of some genes such as Glut-1, p53, p21 or Bcl-2, is HIF-1α dependent, whereas expression of others, such as p27, GADD 153 or HO-1, is HIF-1α independent. EPAS-1 and HIF-3α have also been shown to form heterodimeric complexes with Arnt 1 in response to hypoxia.
