Life SciencesMolecular BiologyPhysiologyGene ExpressionMetabolismSignal TransductionCellular Responses To HypoxiaHypoxia AdaptationHypoxia PhysiologyOxidative StressRedox MetabolismRedox SignalingCellular Hypoxia SignalingCellular Oxygen HomeostasisHif-1 SignalingHypoxia-induced Gene ExpressionHypoxia-inducible Factor RegulationHypoxia-inducible Factor SignalingOxygenationTranscriptional Responses To Hypoxia
The survival of all metazoan organisms is dependent on the regulation of O2 delivery and utilization to maintain a balance between the generation of energy and production of potentially toxic oxidants. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis and has essential roles in metazoan development, physiology, and disease pathogenesis. Remarkable progress has been made in delineating the molecular mechanisms whereby changes in cellular oxygenation are transduced to the nucleus as changes in gene transcription through the activity of HIF-1. Pharmacologic agents that activate or inhibit the hypoxia signal transduction pathway may be useful therapies for ischemic and neoplastic disorders, respectively, which are the major causes of mortality in industrialized societies.
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A Conserved Family of Prolyl-4-Hydroxylases That Modify HIF
Richard K. Bruick, Steven L. McKnight · Science · 2001 · 2.5K citations
Erik Laughner, Panthea Taghavi, Kelly A. Chiles et al. · Molecular and Cellular Biology · 2001 · 1.3K citations · Full text