MECHANISMS OF SIGNAL TRANSDUCTION
Rac1 Activity Is Required for the Activation of Hypoxia-inducible Factor 1*

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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.

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Published, JBC Papers in Press, March 30, 2001, DOI 10.1074/jbc.M100677200

*

This work was supported in part by National Institutes of Health Grants R01-HL55338 and R01-DK39869 (to G. L. S.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported in part by the Yamanouchi Foundation for Research on Metabolic Disorders and by a fellowship from the Uehara Memorial Foundation.

© 2001 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.