Rac1 Activity is Required for the Activation of Hypoxia-inducible Factor 1

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates cellular and systemic homeostatic responses (including erythropoiesis, angiogenesis, and glycolysis) to reduced O₂, availability in mammals. Hypoxia induces both the protein expression and transcriptional activity of the HIF-1α subunit. However, the molecular mechanisms of sensing and signal transduction by which changes in O₂ concentration result in changes in HIF-1 activity are poorly understood. We report here that the small GTPase Rac1 is activated in response to hypoxia and is required for the induction of HIF-1α protein expression and transcriptional activity in hypoxic cells.