HIF-1: mediator of physiological and pathophysiological responses to hypoxia

Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension.

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The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis

Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180

The Biology of Vascular Endothelial Growth Factor

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Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1

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A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation

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Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis

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Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α

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Regulation of hypoxia-inducible factor 1α is mediated by an O 2 -dependent degradation domain via the ubiquitin-proteasome pathway

Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.7987 · Cited by 2,113

Purification and Characterization of Hypoxia-inducible Factor 1

Wang, G. L., & Semenza, G. L. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.3.1230 · Cited by 2,094

Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1

Semenza, G. L., Jiang, B.-H., Leung, S. W., Passantino, R., Concordet, J.-P., Maire, P., & Giallongo, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32529 · Cited by 1,752

Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix.

Höckel, M., Schlenger, K., Aral, B., Mitze, M., Schäffer, U., & Vaupel, P. W. (1996) · PubMed · Cited by 1,727

Hypoxia-inducible Factor 1α (HIF-1α) Protein Is Rapidly Degraded by the Ubiquitin-Proteasome System under Normoxic Conditions

Salceda, S., & Caro, J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22642 · Cited by 1,674

PAS Domains: Internal Sensors of Oxygen, Redox Potential, and Light

Taylor, B. L., & Zhulin, I. B. (1999) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.63.2.479-506.1999 · Cited by 1,632

HIF‐1α is required for solid tumor formation and embryonic vascularization

Ryan, H. E., Lo, J., & Johnson, R. S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3005 · Cited by 1,579

Positional Cloning of the Mouse Circadian Gene

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Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells.

Tian, H., McKnight, S. L., & Russell, D. W. (1997) · Genes & Development · doi:10.1101/gad.11.1.72 · Cited by 1,351

Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension

Jiang, B. H., Semenza, G. L., Bauer, C., & Marti, H. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.4.c1172 · Cited by 1,213

Activation of Hypoxia-inducible Transcription Factor Depends Primarily upon Redox-sensitive Stabilization of Its α Subunit

Huang, E. L., Arany, Z. P., Livingston, D. M., & Bunn, H. F. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32253 · Cited by 1,204

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Gene Expression Profiles in Normal and Cancer Cells

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Dimerization, DNA Binding, and Transactivation Properties of Hypoxia-inducible Factor 1

Jiang, B.-H., Rue, E., Wang, G. L., Roe, R., & Semenza, G. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.17771 · Cited by 1,106 · cited 1×

Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth

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A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1α regulates the VEGF expression and is potentially involved in lung and vascular development

Ema, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., & Fujii-Kuriyama, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4273 · Cited by 1,016

Cloning of a Factor Required for Activity of the Ah (Dioxin) Receptor

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Structure of the VHL-ElonginC-ElonginB Complex: Implications for VHL Tumor Suppressor Function

Stebbins, C. E., Kaelin, W. G., & Pavletich, N. P. (1999) · Science · doi:10.1126/science.284.5413.455 · Cited by 852

Stabilization of wild-type p53 by hypoxia-inducible factor 1α

An, W. G., Kanekal, M., Simon, M. C., Maltepe, E., Blagosklonny, M. V., & Neckers, L. Μ. (1998) · Nature · doi:10.1038/32925 · Cited by 834

Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor.

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Differential Transcriptional Regulation of the Two Vascular Endothelial Growth Factor Receptor Genes

Gerber, H.-P., Condorelli, F., Park, J., & Ferrara, N. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23659 · Cited by 794

Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia

Lee, P. J., Jiang, B.-H., Chin, B. Y., Iyer, N. V., Alam, J., Semenza, G. L., & Choi, A. K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.9.5375 · Cited by 782

Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT

Maltepe, E., Schmidt, J. V., Baunoch, D., Bradfield, C. A., & Simon, M. C. (1997) · Nature · doi:10.1038/386403a0 · Cited by 781

Desferrioxamine induces erythropoietin gene expression and hypoxia- inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction

Wang, G., & Semenza, G. (1993) · Blood · doi:10.1182/blood.v82.12.3610.3610 · Cited by 766

Regulation of the Hypoxia-inducible Transcription Factor 1α by the Ubiquitin-Proteasome Pathway

Kallio, P. J., Wilson, W. J., O’Brien, S. L., Makino, Y., & Poellinger, L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6519 · Cited by 754

Signal transduction in hypoxic cells: inducible nuclear translocation and recruitment of theCBP/p300 coactivator by the hypoxia‐induciblefactor‐1α

Kallio, P. J., Okamoto, K., O'Brien, S., Carrero, P., Makino, Y., Tanaka, H., & Poellinger, L. (1998) · The EMBO Journal · doi:10.1093/emboj/17.22.6573 · Cited by 669

Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α

Yu, A. Y., Shimoda, L. A., Iyer, N. V., Huso, D. L., Sun, X., McWilliams, R. M., Beaty, T. H., Sham, J. S. K., Wiener, C. M., Sylvester, J. T., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5912 · Cited by 653

The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development

Tian, H., Hammer, R. E., Matsumoto, A. M., Russell, D. W., & McKnight, S. L. (1998) · Genes & Development · doi:10.1101/gad.12.21.3320 · Cited by 647

Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2.

Feldser, D. M., Agani, F. H., Iyer, N. V., Pak, B. J., Ferreira, G., & Semenza, G. L. (1999) · PubMed · Cited by 638

Induction of Endothelial PAS Domain Protein-1 by Hypoxia: Characterization and Comparison With Hypoxia-Inducible Factor-1α

Wiesener, M. S., Turley, H., Allen, W. E., Willam, C., Eckardt, K., Talks, K., Wood, S. M., Gatter, K. C., Harris, A. L., Pugh, C. W., et al. (1998) · Blood · doi:10.1182/blood.v92.7.2260 · Cited by 629

Transactivation and Inhibitory Domains of Hypoxia-inducible Factor 1α

Jiang, B.-H., Zheng, J. Z., Leung, S. W., Roe, R., & Semenza, G. L. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.31.19253 · Cited by 629

A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter.

Melillo, G., Musso, T., Sica, A., Taylor, L. S., Cox, G. W., & Varesio, L. (1995) · The Journal of Experimental Medicine · doi:10.1084/jem.182.6.1683 · Cited by 625

Molecular mechanisms of transcription activation by HLF and HIF1α in response to hypoxia: their stabilization and redox signal‐induced interaction with CBP/p300

Ema, M., Hirota, K., Mimura, J., Abe, H., Yodoi, J., Sogawa, K., Poellinger, L., & Fujii‐Kuriyama, Y. (1999) · The EMBO Journal · doi:10.1093/emboj/18.7.1905 · Cited by 586

Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha.

Gu, Y.-Z., Moran, S. M., Hogenesch, J. B., Wartman, L. D., & Bradfield, C. A. (1998) · Europe PMC (PubMed Central) · Cited by 577

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 progression.

Jiang, B., Agani, F. H., Passaniti, A., & Semenza, G. L. (1997) · PubMed · Cited by 532

Activation of Hypoxia-inducible Factor-1; Definition of Regulatory Domains within the α Subunit

Pugh, C. W., O'Rourke, J. F., Nagao, M., Gleadle, J., & Ratcliffe, P. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.17.11205 · Cited by 526

Characterization of a Subset of the Basic-Helix-Loop-Helix-PAS Superfamily That Interacts with Components of the Dioxin Signaling Pathway

Hogenesch, J. B., Chan, W. K., Jackiw, V., Brown, R. C., Gu, Y.-Z., Pray-Grant, M. G., Perdew, G. H., & Bradfield, C. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8581 · Cited by 514

Identification of the von Hippel–Lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex

Iwai, K., Yamanaka, K., Kamura, T., Minato, N., Conaway, R. C., Conaway, J. W., Klausner, R. D., & Pause, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12436 · Cited by 508

Defective Vascularization of HIF-1α-Null Embryos Is Not Associated with VEGF Deficiency but with Mesenchymal Cell Death

Kotch, L. E., Iyer, N. V., Laughner, E., & Semenza, G. L. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9253 · Cited by 422

In VivoExpression of mRNAs Encoding Hypoxia-Inducible Factor 1

Wiener, C. M., Booth, G., & Semenza, G. L. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1199 · Cited by 413

Induction of hypoxia‐inducible factor‐1 (HIF‐1) and its target genes following focal ischaemia in rat brain

Bergeron, M., Yu, A. Y., Solway, K., Semenza, G. L., & Sharp, F. R. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00845.x · Cited by 410

Oxygen-regulated transferrin expression is mediated by hypoxia-inducible factor-1

Rolfs, A., Kvietikova, I., Gassmann, M., & Wenger, R. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.32.20055 · Cited by 401

Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1Preprint

Bhattacharya, S., Michels, C. L., Leung, M.-K., Arany, Z. P., Kung, A. L., & Livingston, D. M. (1999) · Genes & Development · doi:10.1101/gad.13.1.64 · Cited by 397

Perspectives on Oxygen Sensing

Semenza, G. L. (1999) · Cell · doi:10.1016/s0092-8674(00)81957-1 · Cited by 385

The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activityPreprint

Lisztwan, J. H., Imbert, G., Wirbelauer, C., Gstaiger, M., & Krek, W. (1999) · Genes & Development · doi:10.1101/gad.13.14.1822 · Cited by 380

Identification of a hypoxia response element in the transferrin receptor gene

Lok, C. N., & Ponka, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.24147 · Cited by 380

Transferrin Receptor Induction by Hypoxia

Tacchini, L., Bianchi, L., Bernelli-Zazzera, A., & Cairo, G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.34.24142 · Cited by 379

HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1α and developmentally expressed in blood vessels

Flamme, I., Fröhlich, T., von Reutern, M., Kappel, A., Damert, A., & Risau, W. (1997) · Mechanisms of Development · doi:10.1016/s0925-4773(97)00674-6 · Cited by 373

Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung

Yu, A. Y., Frid, M. G., Shimoda, L. A., Wiener, C. M., Stenmark, K. R., & Semenza, G. L. (1998) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1998.275.4.l818 · Cited by 370

Expression of ARNT, ARNT2, HIF1α, HIF2α and Ah receptor mRNAs in the developing mouse

Jain, S., Maltepe, E., Lu, M. M., Simon, C., & Bradfield, C. A. (1998) · Mechanisms of Development · doi:10.1016/s0925-4773(98)00038-0 · Cited by 333

Hypoxia induces type II NOS gene expression in pulmonary artery endothelial cells via HIF-1

Palmer, L. A., Semenza, G. L., Stoler, M. H., & Johns, R. A. (1998) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1998.274.2.l212 · Cited by 327

Hypoxia inducible factor-1alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression.

Ozaki, H., Yu, A. Y., Della, N. G., Ozaki, K., Luna, J. D., Yamada, H., Hackett, S. F., Okamoto, N., Zack, D. J., Semenza, G. L., et al. (1999) · PubMed · Cited by 323

cDNA Cloning and Tissue-Specific Expression of a Novel Basic Helix-Loop-Helix/PAS Factor (Arnt2) with Close Sequence Similarity to the Aryl Hydrocarbon Receptor Nuclear Translocator (Arnt)

Hirose, K., Morita, M., Ema, M., Mimura, J., Hamada, H., Fujii, H., Saijo, Y., Gotoh, O., Sogawa, K., & Fujii‐Kuriyama, Y. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.4.1706 · Cited by 271

Nitric Oxide Synthase Is the Mediator of Late Preconditioning Against Myocardial Infarction in Conscious Rabbits

Takano, H., Manchikalapudi, S., Tang, X., Qiu, Y., Rizvi, A., Jadoon, A. K., Zhang, Q., & Bolli, R. (1998) · Circulation · doi:10.1161/01.cir.98.5.441 · Cited by 256

Hypoxia Regulates Expression of the Endothelin-1 Gene through a Proximal Hypoxia-Inducible Factor-1 Binding Site on the Antisense Strand

Hu, J. Y., Discher, D. J., Bishopric, N. H., & Webster, K. A. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8543 · Cited by 254

Oxygen-regulated and Transactivating Domains in Endothelial PAS Protein 1: Comparison with Hypoxia-inducible Factor-1α

O'Rourke, J. F., Tian, Y.-M., Ratcliffe, P. J., & Pugh, C. W. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.4.2060 · Cited by 242

Increased expression of hypoxia inducible factor-1alpha in rat and human prostate cancer.

Zhong, H., Agani, F. H., Baccala, A. A., Laughner, E., Rioseco‐Camacho, N., Wb, I., Simons, J. W., & Semenza, G. L. (1998) · PubMed · Cited by 232

Adrenomedullin Gene Expression Is Developmentally Regulated and Induced by Hypoxia in Rat Ventricular Cardiac Myocytes

Cormier, S. A., Nguyen, S. V., & Claycomb, W. C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.28.17787 · Cited by 230

An essential role of NFκB in tyrosine kinase signaling of p38 MAP kinase regulation of myocardial adaptation to ischemia

Maulik, N., Sato, M., Price, B. D., & Das, D. K. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00632-2 · Cited by 229

Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: A possible model for IGFBP-1 expression in fetal hypoxia

Tazuke, S. I., Mazure, N. M., Sugawara, J., Carland, G., Faessen, G. H., Suen, L.-F., Irwin, J. C., Powell, D. R., Giaccia, A. J., & Giudice, L. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10188 · Cited by 222

cDNA Cloning and Tissue-Specific Expression of a Novel Basic Helix–Loop–Helix/PAS Protein (BMAL1) and Identification of Alternatively Spliced Variants with Alternative Translation Initiation Site Usage

Ikeda, M., & Nomura, M. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6371 · Cited by 220

Expression Patterns of Two Murine Homologs ofDrosophila Single-MindedSuggest Possible Roles in Embryonic Patterning and in the Pathogenesis of Down Syndrome

Fan, C., Kuwana, E., Bulfone, A., Fletcher, C., Copeland, N. G., Jenkins, N. A., Crews, S. T., Martı́nez, S., Puelles, L., Rubenstein, J. L. R., et al. (1996) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1996.0037 · Cited by 199

Remembrance of things PAS: regulation of development by bHLH–PAS proteins

Crews, S. T., & Fan, C. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00003-9 · Cited by 198

Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system

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Hypoxia-Inducible Factor-1α Mediates Hypoxia-Induced Delayed Neuronal Death That Involves p53

Halterman, M. W., Miller, C. C., & Federoff, H. J. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-16-06818.1999 · Cited by 191

Selection and Analysis of a Mutant Cell Line Defective in the Hypoxia-inducible Factor-1 α-Subunit (HIF-1α)

Wood, S. M., Wiesener, M. S., Yeates, K. M., Okada, N., Pugh, C. W., Maxwell, P. H., & Ratcliffe, P. J. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.14.8360 · Cited by 189

Expression Patterns of Two Murine Homologs ofDrosophila Single-MindedSuggest Possible Roles in Embryonic Patterning and in the Pathogenesis of Down Syndrome

Fan, C., Kuwana, E., Bulfone, A., Fletcher, C., Copeland, N. G., Jenkins, N. A., Crews, S. T., Martı́nez, S., Puelles, L., Rubenstein, J. L. R., et al. (1996) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1996.0001 · Cited by 164

Transcriptionally Active Heterodimer Formation of an Arnt-like PAS Protein, Arnt3, with HIF-1a, HLF, and Clock

Takahata, S., Sogawa, K., Kobayashi, A., Ema, M., Mimura, J., Ozaki, N., & Fujii‐Kuriyama, Y. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9012 · Cited by 153

Cardiac hypertrophy in chronically anemic fetal sheep: Increased vascularization is associated with increased myocardial expression of vascular endothelial growth factor and hypoxia-inducible factor 1

Martin, C., Yu, A. Y., Jiang, B., Davis, L. E., Kimberly, D. J., Hohimer, A. R., & Semenza, G. L. (1998) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(98)70433-8 · Cited by 145

Nucleotide Sequence, Chromosomal Assignment and mRNA Expression of Mouse Hypoxia-Inducible Factor-1α

Wenger, R. H., Rolfs, A., Marti, H. H., Guénet, J., & Gassmann, M. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0845 · Cited by 122

Characterization of the α 1B -adrenergic receptor gene promoter region and hypoxia regulatory elements in vascular smooth muscle

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Transcription Factors and Human Disease

Semenza, G. L. (1998) · Cited by 39

Oxygen regulation of ion channels and gene expression

López‐Barneo, J., & Weir, Ε. K. (1998) · Medical Entomology and Zoology · Cited by 20

Free radicals and antioxidants in normal physiological functions and human disease

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Free Radicals in the Physiological Control of Cell Function

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Free radicals, metals and antioxidants in oxidative stress-induced cancer

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C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation

Epstein, A. C. R., Gleadle, J. M., McNeill, L. A., Hewitson, K. S., O'Rourke, J., Mole, D. R., Mukherji, M., Metzen, E., Wilson, M. I., Dhanda, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00507-4 · Cited by 3,333

VEGF in signaling and disease: beyond discovery and development

Apte, R. S., Chen, D. S., & Ferrara, N. (2019) · Cell · doi:10.1016/j.cell.2019.01.021 · Cited by 2,721

HIF-1: a key mediator in hypoxia (Review)

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Hypoxia, HIF-1, and the Pathophysiologi of Common Human Diseases

Semenza, G. L., Agani, F., Feldser, D., Lyer, N., Kotch, L., Laughner, E., & Yu, 1. (2006) · Advances in Experimental Medicine and Biology · doi:10.1007/0-306-46825-5_12 · Cited by 241

Regulation of Mammalian O 2 Homeostasis by Hypoxia-Inducible Factor 1

Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914

Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1

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Life with Oxygen

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