Tissue hypoxia is a pathologic feature of many human diseases including cancer,
myocardial infarction, stroke, and kidney disease. An evolutionarily conserved oxygen-
sensing mechanism enables cells to adapt and maintain homeostasis under hypoxic
conditions by transcriptional activation of a host of genes that mediate metabolic adaptation,
angiogenesis, energy conservation, erythropoiesis, and cell survival. The hypoxia-inducible
factors (HIFs) comprise a family of oxygen-sensitive basic helix-loop-helix proteins that …