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(The FASEB Journal. 2002;16:1151-1162.)
© 2002 FASEB

Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression

ROLAND H. WENGER

Carl-Ludwig-Institute of Physiology, University of Leipzig, Leipzig, Germany

1Correspondence: Carl-Ludwig-Institute of Physiology, University of Leipzig, Liebigstrasse 27, D-04103 Leipzig, Germany. E-mail: wenr{at}medizin.uni-leipzig.de

Although it was known for a long time that oxygen deprivation leads to the transcriptional induction of the gene encoding erythropoietin, the molecular mechanisms behind this process remained enigmatic. The cloning of the hypoxia-inducible factors (HIFs), the finding that HIF-1 regulates the expression of many more genes apart from erythropoietin, and the elucidation of the oxygen-dependent mechanisms degrading the HIF {alpha} subunits recently led to the spectacular discovery of the molecular principles of oxygen sensing. This review aims to summarize our current knowledge of oxygen-regulated gene expression.—Wenger, R. H. Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression.


Key Words: environmental adaptation • erythropoietin • oxygen • transcriptional regulation • vascular endothelial growth factor




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