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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
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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R. H. Wenger, D. P. Stiehl, and G. Camenisch Integration of Oxygen Signaling at the Consensus HRE Sci. Signal., October 18, 2005; 2005(306): re12 - re12. [Abstract] [Full Text] [PDF] |
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J. An and M. B. Rettig Mechanism of von Hippel-Lindau Protein-Mediated Suppression of Nuclear Factor kappa B Activity Mol. Cell. Biol., September 1, 2005; 25(17): 7546 - 7556. [Abstract] [Full Text] [PDF] |
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L. Li, X. Lin, M. Staver, A. Shoemaker, D. Semizarov, S. W. Fesik, and Y. Shen Evaluating Hypoxia-Inducible Factor-1{alpha} as a Cancer Therapeutic Target via Inducible RNA Interference In vivo Cancer Res., August 15, 2005; 65(16): 7249 - 7258. [Abstract] [Full Text] [PDF] |
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A. A. Kazi, J. M. Jones, and R. D. Koos Chromatin Immunoprecipitation Analysis of Gene Expression in the Rat Uterus in Vivo: Estrogen-Induced Recruitment of Both Estrogen Receptor {alpha} and Hypoxia-Inducible Factor 1 to the Vascular Endothelial Growth Factor Promoter Mol. Endocrinol., August 1, 2005; 19(8): 2006 - 2019. [Abstract] [Full Text] [PDF] |
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E. Temes, S. Martin-Puig, B. Acosta-Iborra, M. C. Castellanos, M. Feijoo-Cuaresma, G. Olmos, J. Aragones, and M. O. Landazuri Activation of HIF-prolyl Hydroxylases by R59949, an Inhibitor of the Diacylglycerol Kinase J. Biol. Chem., June 24, 2005; 280(25): 24238 - 24244. [Abstract] [Full Text] [PDF] |
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F. Martin, T. Linden, D. M. Katschinski, F. Oehme, I. Flamme, C. K. Mukhopadhyay, K. Eckhardt, J. Troger, S. Barth, G. Camenisch, et al. Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation Blood, June 15, 2005; 105(12): 4613 - 4619. [Abstract] [Full Text] [PDF] |
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C. Shen, D. Nettleton, M. Jiang, S. K. Kim, and J. A. Powell-Coffman Roles of the HIF-1 Hypoxia-inducible Factor during Hypoxia Response in Caenorhabditis elegans J. Biol. Chem., May 27, 2005; 280(21): 20580 - 20588. [Abstract] [Full Text] [PDF] |
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A. Ozer, L. C. Wu, and R. K. Bruick The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF) PNAS, May 24, 2005; 102(21): 7481 - 7486. [Abstract] [Full Text] [PDF] |
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R. Helton, J. Cui, J. R. Scheel, J. A. Ellison, C. Ames, C. Gibson, B. Blouw, L. Ouyang, I. Dragatsis, S. Zeitlin, et al. Brain-Specific Knock-Out of Hypoxia-Inducible Factor-1{alpha} Reduces Rather Than Increases Hypoxic-Ischemic Damage J. Neurosci., April 20, 2005; 25(16): 4099 - 4107. [Abstract] [Full Text] [PDF] |
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E. B. Rankin, D. F. Higgins, J. A. Walisser, R. S. Johnson, C. A. Bradfield, and V. H. Haase Inactivation of the Arylhydrocarbon Receptor Nuclear Translocator (Arnt) Suppresses von Hippel-Lindau Disease-Associated Vascular Tumors in Mice Mol. Cell. Biol., April 15, 2005; 25(8): 3163 - 3172. [Abstract] [Full Text] [PDF] |
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H. Yun, M. Lee, S.-S. Kim, and J. Ha Glucose Deprivation Increases mRNA Stability of Vascular Endothelial Growth Factor through Activation of AMP-activated Protein Kinase in DU145 Prostate Carcinoma J. Biol. Chem., March 18, 2005; 280(11): 9963 - 9972. [Abstract] [Full Text] [PDF] |
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S. McMahon, F. Grondin, P. P. McDonald, D. E. Richard, and C. M. Dubois Hypoxia-enhanced Expression of the Proprotein Convertase Furin Is Mediated by Hypoxia-inducible Factor-1: IMPACT ON THE BIOACTIVATION OF PROPROTEINS J. Biol. Chem., February 25, 2005; 280(8): 6561 - 6569. [Abstract] [Full Text] [PDF] |
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G. Yuan, J. Nanduri, C. R. Bhasker, G. L. Semenza, and N. R. Prabhakar Ca2+/Calmodulin Kinase-dependent Activation of Hypoxia Inducible Factor 1 Transcriptional Activity in Cells Subjected to Intermittent Hypoxia J. Biol. Chem., February 11, 2005; 280(6): 4321 - 4328. [Abstract] [Full Text] [PDF] |
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J. M. Lluis, A. Morales, C. Blasco, A. Colell, M. Mari, C. Garcia-Ruiz, and J. C. Fernandez-Checa Critical Role of Mitochondrial Glutathione in the Survival of Hepatocytes during Hypoxia J. Biol. Chem., February 4, 2005; 280(5): 3224 - 3232. [Abstract] [Full Text] [PDF] |
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S. Kajimura, K. Aida, and C. Duan From the Cover: Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation PNAS, January 25, 2005; 102(4): 1240 - 1245. [Abstract] [Full Text] [PDF] |
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S. R. Walmsley, C. Print, N. Farahi, C. Peyssonnaux, R. S. Johnson, T. Cramer, A. Sobolewski, A. M. Condliffe, A. S. Cowburn, N. Johnson, et al. Hypoxia-induced neutrophil survival is mediated by HIF-1{alpha}-dependent NF-{kappa}B activity J. Exp. Med., January 3, 2005; 201(1): 105 - 115. [Abstract] [Full Text] [PDF] |
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Q. Liu, U. Moller, D. Flugel, and T. Kietzmann Induction of plasminogen activator inhibitor I gene expression by intracellular calcium via hypoxia-inducible factor-1 Blood, December 15, 2004; 104(13): 3993 - 4001. [Abstract] [Full Text] [PDF] |
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W. K. Rathmell, M. M. Hickey, N. A. Bezman, C. A. Chmielecki, N. C. Carraway, and M. C. Simon In vitro and In vivo Models Analyzing von Hippel-Lindau Disease-Specific Mutations Cancer Res., December 1, 2004; 64(23): 8595 - 8603. [Abstract] [Full Text] [PDF] |
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J.-T. Hwang, M. Lee, S.-N. Jung, H.-J. Lee, I. Kang, S.-S. Kim, and J. Ha AMP-activated protein kinase activity is required for vanadate-induced hypoxia-inducible factor 1{alpha} expression in DU145 cells Carcinogenesis, December 1, 2004; 25(12): 2497 - 2507. [Abstract] [Full Text] [PDF] |
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N. Morita, K. Iizuka, K. Okita, T. Oikawa, K. Yonezawa, T. Nagai, Y. Tokumitsu, T. Murakami, A. Kitabatake, and H. Kawaguchi Exposure to pressure stimulus enhances succinate dehydrogenase activity in L6 myoblasts Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1064 - E1069. [Abstract] [Full Text] [PDF] |
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G. Chachami, G. Simos, A. Hatziefthimiou, S. Bonanou, P.-A. Molyvdas, and E. Paraskeva Cobalt Induces Hypoxia-Inducible Factor-1{alpha} Expression in Airway Smooth Muscle Cells by a Reactive Oxygen Species- and PI3K-Dependent Mechanism Am. J. Respir. Cell Mol. Biol., November 1, 2004; 31(5): 544 - 551. [Abstract] [Full Text] [PDF] |
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J.-M. Li and A. M Shah Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1014 - R1030. [Abstract] [Full Text] [PDF] |
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