Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 31, Issue 7, Pages 847-855Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0891-5849(01)00657-8
Keywords
hypoxia; hypoxia-inducible factor-1; mitogen-activated protein kinases; phosphoinositide-3 kinase; signaling; tumorigenesis; free radicals
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Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor which is activated by hypoxia and involved in the adaptative response of the cell to oxygen deprivation. During hypoxic stress, HIF-1 triggers the overexpression of genes coding for glycolytic enzymes and angiogenic factors. To be active HIF-1 must be phosphorylated. HIF-1 is a substrate for various kinase pathways including PI-3K and the MAP kinases ERK and p38. Several transduction pathways have been proposed which act downstream of putative oxygen sensors and lead to the activation of these kinases. In this review, we summarize some of the latest advances describing the possible signaling pathways leading to HIF-1 phosphorylation and subsequent activation. The physiological relevance of these regulations is also discussed. (C) 2001 Elsevier Science Inc.
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