Research Topics
Genomes and Genes
| G L SemenzaSummaryAffiliation: Johns Hopkins University Country: USA Publications
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Detail Information
Publications
Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1G L Semenza
Center for Medical Genetics, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
J Biol Chem 271:32529-37. 1996..These results provide further evidence that the coordinate transcriptional activation of genes encoding glycolytic enzymes which occurs in hypoxic cells is mediated by HIF-1...- V-SRC induces expression of hypoxia-inducible factor 1 (HIF-1) and transcription of genes encoding vascular endothelial growth factor and enolase 1: involvement of HIF-1 in tumor progressionB H Jiang
Center for Medical Genetics, Department of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Cancer Res 57:5328-35. 1997..These studies link an oncogene to the induction of HIF-1 expression, thus providing a mechanism for hypoxic adaptation by tumor cells... - Mersalyl is a novel inducer of vascular endothelial growth factor gene expression and hypoxia-inducible factor 1 activityF Agani
Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Mol Pharmacol 54:749-54. 1998.... - Defective vascularization of HIF-1alpha-null embryos is not associated with VEGF deficiency but with mesenchymal cell deathL E Kotch
Institute of Genetic MedicineDepartment of PediatricsDepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287 3914, USA
Dev Biol 209:254-67. 1999..Rather than being associated with VEGF deficiency, the vascular defects in Hif1a-/- embryos were spatially correlated with cell death, the onset of which preceded vascular regression... - HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expressionE Laughner
Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA
Mol Cell Biol 21:3995-4004. 2001..These data provide a molecular basis for VEGF induction and tumor angiogenesis by heregulin-HER2 signaling and establish a novel mechanism for the regulation of HIF-1alpha expression... - Transactivation and inhibitory domains of hypoxia-inducible factor 1alpha. Modulation of transcriptional activity by oxygen tensionB H Jiang
Center for Medical Genetics, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
J Biol Chem 272:19253-60. 1997..These results indicate that increased transcriptional activity mediated by HIF-1 in hypoxic cells results from both increased HIF-1alpha protein levels and increased activity of HIF-1alpha transactivation domains... - Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1J A Forsythe
Department of Physiology, University of Maryland School of Medicine, Baltimore, 21201, USA
Mol Cell Biol 16:4604-13. 1996..VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells... - Hypoxia-inducible factor 1alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutationsC H Sutter
Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287 3914, USA
Proc Natl Acad Sci U S A 97:4748-53. 2000..We demonstrate that hypoxia results in decreased ubiquitination of HIF-1alpha and that missense mutations increase HIF-1alpha expression under nonhypoxic conditions by blocking ubiquitination... - Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alphaN V Iyer
Center for Medical Genetics, Departments of Pediatrics and Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914 USA
Genes Dev 12:149-62. 1998..5 and E9.5, coincident with the onset of developmental defects and cell death in Hif1a-/- embryos. These results demonstrate that HIF-1alpha is a master regulator of cellular and developmental O2 homeostasis... - Oxygen-independent upregulation of vascular endothelial growth factor and vascular barrier dysfunction during ventilated pulmonary ischemia in isolated ferret lungsP M Becker
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Am J Respir Cell Mol Biol 22:272-9. 2000..These results implicate VEGF as a potential mediator of increased pulmonary vascular permeability in this model of acute lung injury... - FIH-1: a novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activityP C Mahon
Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Genes Dev 15:2675-86. 2001..Involvement of VHL in association with FIH-1 provides a unifying mechanism for the modulation of HIF-1alpha protein stabilization and transcriptional activation in response to changes in cellular O(2) concentration... - General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxiaG L Wang
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205
Proc Natl Acad Sci U S A 90:4304-8. 1993..These results provide evidence that HIF-1 and its recognition sequence are common components of a general mammalian cellular response to hypoxia... - Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1B H Jiang
Center for Medical Genetics, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
J Biol Chem 271:17771-8. 1996..Overexpression of a HIF-1alpha construct with deletions of the basic domain and carboxy terminus blocked reporter gene activation by endogenous HIF-1 in hypoxic cells... - Oncogenic alterations of metabolismC V Dang
Dept of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Trends Biochem Sci 24:68-72. 1999.... - Regulation of cardiovascular development and physiology by hypoxia-inducible factor 1G L Semenza
Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Ann N Y Acad Sci 874:262-8. 1999.... - The human hypoxia-inducible factor 1alpha gene: HIF1A structure and evolutionary conservationN V Iyer
Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA
Genomics 52:159-65. 1998..The proximal 300 bp of 5' flanking sequences was 83% identical, including the SP1 sites and transcription initiation sites. These results suggest evolutionary selection for maintenance of HIF1A structure, function, and regulation... - Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tensionG L Wang
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287 3914, USA
Proc Natl Acad Sci U S A 92:5510-4. 1995.... - Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1G L Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914
J Biol Chem 269:23757-63. 1994..These results support the role of HIF-1 as a mediator of adaptive responses to hypoxia that underlie cellular and systemic oxygen homeostasis... - Partial HIF-1alpha deficiency impairs pulmonary arterial myocyte electrophysiological responses to hypoxiaL A Shimoda
Division of Pulmonary and Critical Care Medicine and Institute of Genetic Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21224, USA
Am J Physiol Lung Cell Mol Physiol 281:L202-8. 2001..Thus partial deficiency of HIF-1alpha is sufficient to impair hypoxia-induced depolarization, reduction of K+ current density, and PASMC hypertrophy... - Expression of hypoxia-inducible factor 1: mechanisms and consequencesG L Semenza
The Johns Hopkins School of Medicine, Baltimore, MD 21287 3914, USA
Biochem Pharmacol 59:47-53. 2000..Pharmacologic manipulation of HIF-1 levels may provide a novel therapeutic approach to diseases that represent the most common causes of mortality in Western society, including cancer, chronic lung disease, and myocardial ischemia... - Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1G L Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Annu Rev Cell Dev Biol 15:551-78. 1999..HIF-1 thus appears to function as a master regulator of O2 homeostasis that plays essential roles in cellular and systemic physiology, development, and pathophysiology... - HIF-1: using two hands to flip the angiogenic switchG L Semenza
Institute of Genetic Medicine, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
Cancer Metastasis Rev 19:59-65. 2000.... - Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxiaP J Lee
Division of Pulmonary and Critical Care, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
J Biol Chem 272:5375-81. 1997..Taken together, these data demonstrate that hypoxia induces HO-1 expression in animal tissues and cell cultures and implicate HIF-1 in this response... - HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleusG L Semenza
McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
Cell 107:1-3. 2001..A molecular basis for O(2)-regulated expression of the HIF-1 alpha subunit has now been determined, providing a mechanism for changes in gene expression in response to changes in cellular oxygenation... - Hypoxia-inducible factor 1: master regulator of O2 homeostasisG L Semenza
Institute for Genetic Medicine, CMSC 1004, The Johns Hopkins UniversitySchool of Medicine, 600 N Wolfe St, Baltimore, Maryland 21287 3914, USA
Curr Opin Genet Dev 8:588-94. 1998..Recent studies have provided insights into the O2-dependent regulation of HIF-1 expression, target genes regulated by HIF-1, and the effects of HIF-1 deficiency on cellular physiology and embryonic development... - Assignment of the hypoxia-inducible factor 1alpha gene to a region of conserved synteny on mouse chromosome 12 and human chromosome 14qG L Semenza
Center for Medical Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287, USA
Genomics 34:437-9. 1996..33... - Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1alphaA Y Yu
Institute of Genetic Medicine, Division of Pulmonary and Critical Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
J Clin Invest 103:691-6. 1999..These results indicate that partial HIF-1alpha deficiency has significant effects on multiple systemic responses to chronic hypoxia... - Purification and characterization of hypoxia-inducible factor 1G L Wang
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914
J Biol Chem 270:1230-7. 1995..We conclude that in both cobalt chloride-treated HeLa cells and hypoxic Hep3B cells HIF-1 is composed of two different subunits: 120-kDa HIF-1 alpha and 91-94-kDa HIF-1 beta... - Hypoxia, clonal selection, and the role of HIF-1 in tumor progressionG L Semenza
Institute of Genetic Medicine, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Crit Rev Biochem Mol Biol 35:71-103. 2000.... - 'The metabolism of tumours': 70 years laterG L Semenza
Institute of Genetic Medicine, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Novartis Found Symp 240:251-60; discussion 260-4. 2001..In human breast cancer and brain tumours, HIF-1alpha overexpression is strongly correlated with tumour grade and vascularity... - HIF-1: mediator of physiological and pathophysiological responses to hypoxiaG L Semenza
Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287 3914, USA
J Appl Physiol 88:1474-80. 2000..Genetic or pharmacological modulation of HIF-1 activity in vivo may represent a novel therapeutic approach to these disorders... - Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiologyG L Semenza
Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Johns Hopkins Hospital, CMSC 1004, 600 North Wolfe Street, Baltimore, MD 21287 3914, USA
Trends Mol Med 7:345-50. 2001..Modulation of HIF-1 activity by genetic or pharmacological means could provide a novel therapeutic approach to these common causes of mortality... - Hypoxia-inducible factor 1: control of oxygen homeostasis in health and diseaseG L Semenza
Institute of Genetic Medicine and Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Pediatr Res 49:614-7. 2001..HIF-1 may also mediate the protective response to cerebral ischemia known as late-phase preconditioning... - In vivo expression of mRNAs encoding hypoxia-inducible factor 1C M Wiener
Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Biochem Biophys Res Commun 225:485-8. 1996..The ubiquitous in vivo expression of HIF-1 alpha and HIF-1 beta (ARNT) mRNA is consistent with the proposed role of HIF-1 in coordinating adaptive transcriptional responses to hypoxia... - Oxygen-regulated transcription factors and their role in pulmonary diseaseG L Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Respir Res 1:159-62. 2000..Angiotensin II induces HIF-1 expression and hypertrophy of pulmonary arterial smooth muscle cells. HIF-1 might therefore have multiple roles in the pathogenesis of pulmonary vascular remodeling... - Hypoxia inhibits G1/S transition through regulation of p27 expressionL B Gardner
Department of Medicine, The Johns Hopkins Oncology Center, Baltimore, Maryland 21205, USA
J Biol Chem 276:7919-26. 2001..This demonstration of the molecular mechanism of hypoxia-induced G1/S regulation provides insight into a fundamental response of mammalian cells to low oxygen tension... - DNA binding and transcriptional properties of wild-type and mutant forms of the homeodomain protein Msx2G L Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 3914, USA
Biochem Biophys Res Commun 209:257-62. 1995..These results provide evidence that Msx2 is a transcriptional repressor and suggest that the mutant form of Msx2 may exert its pathophysiologic effects on craniofacial development by a gain-of-function mechanism... - HIF-1 and mechanisms of hypoxia sensingG L Semenza
Johns Hopkins Hospital, CMSC 1004, 600 North Wolfe Street, Baltimore, Maryland 21287 3914, USA
Curr Opin Cell Biol 13:167-71. 2001..The signal transduction pathway remains enigmatic, but involves generation of reactive oxygen species. Nitric oxide induces HIF-1 alpha under non-hypoxic conditions but inhibits hypoxia-induced HIF-1 alpha expression... - HIF-1 inhibitors for cancer therapy: from gene expression to drug discoveryG L Semenza
The Johns Hopkins University Schoolof Medicine, Baltimore, MD 21205, USA
Curr Pharm Des 15:3839-43. 2009.... - Hypoxia and human disease-and the Journal of Molecular MedicineG L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD, 21205, USA
J Mol Med 85:1293-4. 2007 - Perspectives on oxygen sensingG L Semenza
Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA
Cell 98:281-4. 1999 - A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activationG L Semenza
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Mol Cell Biol 12:5447-54. 1992..We have thus defined a functionally tripartite, 50-nt hypoxia-inducible enhancer which binds several nuclear factors, one of which is induced by hypoxia via de novo protein synthesis... - Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeuticsG L Semenza
Vascular Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Oncogene 29:625-34. 2010.... - Up-regulation of gene expression by hypoxia is mediated predominantly by hypoxia-inducible factor 1 (HIF-1)A E Greijer
Department of Pathology, VUMC, Amsterdam, The Netherlands
J Pathol 206:291-304. 2005..In conclusion, hypoxia causes down- rather than up-regulation of gene expression and HIF-1 seems to play a major role in the regulation of hypoxia-induced genes... - Levels of hypoxia-inducible factor-1 alpha during breast carcinogenesisR Bos
Department of Pathology, Free University Hospital, Amsterdam, The Netherlands
J Natl Cancer Inst 93:309-14. 2001..Increased levels of HIF-1 alpha are associated with increased proliferation and increased expression of ER and VEGF. Thus, increased levels of HIF-1 alpha are potentially associated with more aggressive tumors... - Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: evidence for a process of disordered angiogenesisR M Tuder
Department of Pathology, Division of Pulmonary Sciences and Critical Care Medicine, Pulmonary Hypertension Center, University of Colorado Health Sciences Center, Colorado, USA
J Pathol 195:367-74. 2001..Because markers of angiogenesis are expressed in plexiform lesions in SPH, it is proposed that these lesions may form by a process of disordered angiogenesis... - Rac1 activity is required for the activation of hypoxia-inducible factor 1K Hirota
Department of Anesthesia, Kyoto University Hospital, Kyoto University, Kyoto 606-8507, Japan
J Biol Chem 276:21166-72. 2001..We report here that the small GTPase Rac1 is activated in response to hypoxia and is required for the induction of HIF-1alpha protein expression and transcriptional activity in hypoxic cells... - Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alphaR Ravi
Johns Hopkins Oncology Center, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287 USA
Genes Dev 14:34-44. 2000..These results indicate that amplification of normal HIF-1-dependent responses to hypoxia via loss of p53 function contributes to the angiogenic switch during tumorigenesis... - Expression of hypoxia-inducible factor-1alpha: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancerD M Aebersold
Department of Radiation Oncology, University of Bern, Switzerland
Cancer Res 61:2911-6. 2001.... - Oxygen sensing in the bodyS Lahiri
Department of Physiology, University of Pennsylvania Medical Center, Philadelphia, 19104 6085, USA
Prog Biophys Mol Biol 91:249-86. 2006..Carotid body contains all kinds of transmitters, and an interplay between them must occur. But very little has come to be known as yet. Glimpses of these interactions are evident in the discussion in the last section (Prabhakar)... - SAG/ROC2/RBX2 is a HIF-1 target gene that promotes HIF-1 alpha ubiquitination and degradationM Tan
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109 096, USA
Oncogene 27:1404-11. 2008..Induced SAG then promotes HIF-1alpha ubiquitination and degradation. This feedback loop may serve as a cellular defensive mechanism to reduce potential cytotoxic effects of prolonged HIF-1 activation under hypoxia... - Reversible inhibition of hypoxia-inducible factor 1 activation by exposure of hypoxic cells to the volatile anesthetic halothaneT Itoh
Department of Anesthesia, Kyoto University Hospital, Kyoto University, Kyoto 606-8507, Japan
FEBS Lett 509:225-9. 2001..Halothane reversibly blocks hypoxia-induced HIF-1alpha protein accumulation and transcriptional activity at clinically relevant doses...