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Science 318 (5847): 62-64

Copyright © 2007 by the American Association for the Advancement of Science

Life with Oxygen

Gregg L. Semenza

Abstract: 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.

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}

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Commentary: Antioxidants for Cancer: New Tricks for an Old Dog?.
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Reduction in ovulation or male sex phenotype increases long-term anoxia survival in a daf-16-independent manner in Caenorhabditis elegans.
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PNAS 105, 19426-19431
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J. Physiol. 586, 4055-4059
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Hypoxia-Inducible Factor-1 Is Central to Cardioprotection: A New Paradigm for Ischemic Preconditioning.
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Haematologica 93, 963-967
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Hypoxic Inhibition of Nonsense-Mediated RNA Decay Regulates Gene Expression and the Integrated Stress Response.
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Mitochondria, oxygen sensing, and the regulation of HIF-2{alpha}. Focus on "Induction of HIF-2{alpha} is dependent on mitochondrial O2 consumption in an O2-sensitive adrenomedullary chromaffin cell line".
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Am J Physiol Cell Physiol 294, C1300-C1302
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Blood 111, 5400-5402
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Nucleic Acids Res. 36, 2024-2031
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Interaction with factor inhibiting HIF-1 defines an additional mode of cross-coupling between the Notch and hypoxia signaling pathways.
X. Zheng, S. Linke, J. M. Dias, X. Zheng, K. Gradin, T. P. Wallis, B. R. Hamilton, M. Gustafsson, J. L. Ruas, S. Wilkins, et al. (2008)
PNAS 105, 3368-3373
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Somatic mutations of JAK2 exon 12 as a molecular basis of erythrocytosis.
M. Cazzola (2007)
Haematologica 92, 1585-1589
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