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 O-2 availability in mammals. Hypoxia induces both the protein expression and transcriptional activity of the HIF-1 alpha subunit. However, the molecular mechanisms of sensing and signal transduction by which changes in O-2 concentration result in changes in HIF-1 activity are poorly understood. We report here that the small GTPase Rad is activated in response to hypoxia and is required for the induction of HIF-1 alpha protein expression and transcriptional activity in hypoxic cells.