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-1alpha 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 Rac1 is activated in response to hypoxia and is required for the induction of HIF-1alpha protein expression and transcriptional activity in hypoxic cells.