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Abstract:
The survival of all metazoan organisms is dependent on the regulationof O2 delivery and utilization to maintain a balance betweenthe generation of energy and production of potentially toxicoxidants. Hypoxia-inducible factor 1 (HIF-1) is a transcriptionfactor that functions as a master regulator of oxygen homeostasisand has essential roles in metazoan development, physiology,and disease pathogenesis. Remarkable progress has been madein delineating the molecular mechanisms whereby changes in cellularoxygenation are transduced to the nucleus as changes in genetranscription through the activity of HIF-1. Pharmacologic agentsthat activate or inhibit the hypoxia signal transduction pathwaymay be useful therapies for ischemic and neoplastic disorders,respectively, which are the major causes of mortality in industrializedsocieties.
Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, Radiation Oncology; and McKusick-Nathans Institute of Genetic Medicine; The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, USA. E-mail: gsemenza{at}jhmi.edu
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