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

Abstract

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.