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

Tian, H; McKnight, S L; Russell, D W

doi:10.1101/gad.11.1.72

Cited by 1,351Angiogenesis and VEGF in CancerCancer, Hypoxia, and MetabolismKruppel-like factors research

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

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Tian, H, McKnight, S L, Russell, D W·1997·Genes & Development

DOI 10.1101/gad.11.1.72

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Abstract

Here we describe the cloning and characterization of a PAS domain transcription factor termed endothelial PAS-1 (EPAS1). This protein shares 48% sequence identity with hypoxia inducible factor (HIF-1alpha) and lesser similarity with other members of the basic helix-loop-helix/PAS domain family of transcription factors. Like HIF-1alpha, EPAS1 binds to and activates transcription from a DNA element originally isolated from the erythropoietin gene and containing the sequence 5'-GCCCTACGTGCTGTCTCA-3'. Activation by both HIF-1alpha and EPAS1 is stimulated by hypoxic conditions. EPAS1 forms a heterodimeric complex with the aryl hydrocarbon nuclear transporter prior to transcriptional activation of target genes. EPAS1 expression is limited to the endothelium of mouse embryos and, in agreement with its cell type-specific expression pattern, is capable of specifically activating the transcription of the endothelial tyrosine kinase gene Tie-2. These observations raise the possibility that EPAS1 may represent an important regulator of vascularization, perhaps involving the regulation of endothelial cell gene expression in response to hypoxia.

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Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981 · see citing works
The Aryl Hydrocarbon Receptor Complex
Hankinson, O. (1995) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.35.040195.001515 · Cited by 1,649 · see citing works
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 · see citing works
AH RECEPTOR SIGNALING PATHWAYS
Schmidt, J. V., & Bradfield, C. A. (1996) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.12.1.55 · Cited by 899 · see citing works
Identification of Functional Domains of the Aryl Hydrocarbon Receptor
Fukunaga, B. N., Probst, M. R., Reisz-Porszasz, S., & Hankinson, O. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.49.29270 · Cited by 338 · see citing works

Flagged first, then by citations

Research works printed but not linked: 5

Burbach, K.M., A. Poland, and C.A. Bradfield. 1992. Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc. Natl. Acad. Sci. 89: 8185-8189.
Konopka, R.J. and S. Benzer. 1971. Clock mutants of Drosophila melanogaster. Proc. Natl. Acad. Sci. 68: 2112-2116.
Sato, T.N., Y. Qin, C.A. Kozak, and K.L. Audus. 1993. Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system. Proc. Natl. Acad. Sci. 90: 9355-9358.
Sogawa, K., R. Nakano, A. Kobayashi, Y. Kikuchi, N. Ohe, N. Matsushita, and Y. Fujii-Kuriyama. 1995. Possible function of Ah receptor nuclear translocator (Arnt) homodimer in transcriptional regulation. Proc. Natl. Acad. Sci. 92: 1936- 1940.
Wang, G.L., B.H. Jiang, E.A. Rue, and G.L. Semenza. 1995. Hyp- oxia-inducible factor 1 is a basic-helix-loop-helix-PAS het- erodimer regulated by cellular 02 tension. Proc. Natl. Acad. Sci. 92: 5510-5514.

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Regulation of angiogenesis by hypoxia: role of the HIF system
Pugh, C. W., & Ratcliffe, P. J. (2003) · Nature Medicine · doi:10.1038/nm0603-677 · Cited by 2,520 · see citing works
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476 · see citing works
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 · see citing works
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 · see citing works
HIF-1: mediator of physiological and pathophysiological responses to hypoxia
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HIF1α and HIF2α: sibling rivalry in hypoxic tumour growth and progression
Keith, B., Johnson, R. S., & Simon, M. C. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3183 · Cited by 1,693 · see citing works
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Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions
Chen, Z., Han, F., Du, Y., Shi, H., & Zhou, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01332-8 · Cited by 1,612 · see citing works
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Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002) · Genes & Development · doi:10.1101/gad.991402 · Cited by 1,550 · see citing works
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558 · see citing works
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386 · see citing works
HIF prolyl‐hydroxylase 2 is the key oxygen sensor setting low steady‐state levels of HIF‐1α in normoxia
Berra, E., Benizri, E., Ginouvès, A., Volmat, V., Roux, D., & Pouysségur, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg392 · Cited by 1,348 · see citing works
The Expression and Distribution of the Hypoxia-Inducible Factors HIF-1α and HIF-2α in Normal Human Tissues, Cancers, and Tumor-Associated Macrophages
Talks, K. L., Turley, H., Gatter, K. C., Maxwell, P. H., Pugh, C. W., Ratcliffe, P. J., & Harris, A. L. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64554-3 · Cited by 1,312 · see citing works
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Fukuda, R., Zhang, H., Kim, J.-W., Shimoda, L., Dang, C. V., & Semenza, G. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.047 · Cited by 1,225 · see citing works
Cellular adaptation to hypoxia: O 2 ‐sensing protein hydroxylases, hypoxia‐inducible transcription factors, and O 2 ‐regulated gene expression
Wenger, R. H. (2002) · The FASEB Journal · doi:10.1096/fj.01-0944rev · Cited by 1,135 · see citing works
Hypoxia-inducible factor 1: master regulator of O2 homeostasis
Semenza, G. L. (1998) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(98)80016-6 · Cited by 1,092 · see citing works
Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth
Maxwell, P. H., Dachs, G. U., Gleadle, J. M., Nicholls, L. G., Harris, A. L., Stratford, I. J., Hankinson, O., Pugh, C. W., & Ratcliffe, P. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8104 · Cited by 1,084 · see citing works
Regulation of glycolysis by the hypoxia-inducible factor (HIF): Implications for cellular physiology
Kierans, S. J., & Taylor, C. T. (2021) · The Journal of Physiology · doi:10.1113/jp280572 · Cited by 1,015 · see citing works
Independent function of two destruction domains in hypoxia-inducible factor-α chains activated by prolyl hydroxylation
Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001) · The EMBO Journal · doi:10.1093/emboj/20.18.5197 · Cited by 1,014 · see citing works
Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma
Raval, R. R., Lau, K. W., Tran, M. G. B., Sowter, H. M., Mandriota, S. J., Li, J.-L., Pugh, C. W., Maxwell, P. H., Harris, A. L., & Ratcliffe, P. J. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5675-5686.2005 · Cited by 940 · see citing works
Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology
Semenza, G. L. (2001) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(01)02090-1 · Cited by 930 · see citing works
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Zhang, H., Gao, P., Fukuda, R., Kumar, G., Krishnamachary, B., Zeller, K. I., Dang, C. V., & Semenza, G. L. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.04.001 · Cited by 885 · see citing works
The role of hypoxia-inducible factors in tumorigenesis
Rankin, E. B., & Giaccia, A. J. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.21 · Cited by 806 · see citing works
Targeting renal cell carcinoma with a HIF-2 antagonist
Chen, W., Hill, H., Christie, A., Kim, M. S., Holloman, E., Pavia-Jimenez, A., Homayoun, F., Ma, Y., Patel, N., Yell, P., et al. (2016) · Nature · doi:10.1038/nature19796 · Cited by 709 · see citing works
Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer
Wigerup, C., Påhlman, S., & Bexell, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.009 · Cited by 687 · see citing works
“Semenza and colleagues first described HIF-1α in the nineties (Wang et al., 1995), while Tian et al. (1997) described the second isoform (initially called EPAS1; endothelial PAS protein 1) soon after, findings that were quickly confirmed by several other groups.”
Background
Hypoxia-induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia
Marti, H. J. H., Bernaudin, M., Bellail, A., Schoch, H., Euler, M., Petit, E., & Risau, W. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64964-4 · Cited by 680 · see citing works
Hypoxia-inducible factor 1 and dysregulated c-Myc cooperatively induce vascular endothelial growth factor and metabolic switches hexokinase 2 and pyruvate dehydrogenase kinase 1
Kim, J.-W., Gao, P., Liu, Y.-C., Semenza, G. L., & Dang, C. V. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00440-07 · Cited by 658 · see citing works
Cobalt Inhibits the Interaction between Hypoxia-inducible Factor-α and von Hippel-Lindau Protein by Direct Binding to Hypoxia-inducible Factor-α
Yuan, Y., Hilliard, G., Ferguson, T., & Millhorn, D. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300463200 · Cited by 638 · see citing works
Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs)
Peyssonnaux, C., Zinkernagel, A. S., Schuepbach, R. A., Rankin, E., Vaulont, S., Haase, V. H., Nizet, V., & Johnson, R. S. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31370 · Cited by 639 · see citing works
Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2
Prabhakar, N. R., & Semenza, G. L. (2012) · Physiological Reviews · doi:10.1152/physrev.00030.2011 · Cited by 641 · see citing works
HIF-1 as a target for drug development
Giaccia, A., Siim, B. G., & Johnson, R. S. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1199 · Cited by 631 · see citing works
Passing the baton: the HIF switch
Koh, M. Y., & Powis, G. (2012) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2012.06.004 · Cited by 589 · see citing works
Vascular Endothelial Growth Factor Gene Therapy Increases Survival, Promotes Lung Angiogenesis, and Prevents Alveolar Damage in Hyperoxia-Induced Lung Injury: Evidence That Angiogenesis Participates in Alveolarization
Thébaud, B., Ladha, F., Michelakis, E. D., Sawicka, M., Thurston, G., Eaton, F., Hashimoto, K., Harry, G., Haromy, A., Korbutt, G., et al. (2005) · Circulation · doi:10.1161/circulationaha.105.541524 · Cited by 533 · see citing works
Iron metabolism in the CNS: implications for neurodegenerative diseases
Rouault, T. A. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3453 · Cited by 496 · see citing works
Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1−/− mice.
Scortegagna, M., Ding, K., Oktay, Y., Gaur, A., Thurmond, F., Yan, L.-J., Marck, B. T., Matsumoto, A. M., Shelton, J. M., Richardson, J. A., et al. (2003) · Nature Genetics · doi:10.1038/ng1266 · Cited by 496 · see citing works
Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival
Giatromanolaki, A., Koukourakis, M. I., Sivridis, E., Turley, H., Talks, K., Pezzella, F., Gatter, K. C., & Harris, A. L. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.2018 · Cited by 478 · see citing works
Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation
Imtiyaz, H. Z., Williams, E. P., Hickey, M. M., Patel, S. A., Durham, A. C., Yuan, L.-J., Hammond, R., Gimotty, P. A., Keith, B., & Simon, M. C. (2010) · Journal of Clinical Investigation · doi:10.1172/jci39506 · Cited by 461 · see citing works
Acute postnatal ablation of Hif-2 α results in anemia
Gruber, M., Hu, C.-J., Johnson, R. S., Brown, E. J., Keith, B., & Simon, M. C. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608382104 · Cited by 457 · see citing works
Intestinal Hypoxia-Inducible Transcription Factors Are Essential for Iron Absorption following Iron Deficiency
Shah, Y. M., Matsubara, T., Ito, S., Yim, S.-H., & Gonzalez, F. J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.012 · Cited by 431 · see citing works
Activation of hypoxia-inducible factor 1α: posttranscriptional regulation and conformational change by recruitment of the Arnt transcription factor
Kallio, P. J., Pongratz, I., Gradin, K., McGuire, J., & Poellinger, L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.11.5667 · Cited by 415 · see citing works
Hypoxia-Inducible Factor-1-Dependent Repression of E-cadherin in von Hippel-Lindau Tumor Suppressor–Null Renal Cell Carcinoma Mediated by TCF3, ZFHX1A, and ZFHX1B
Krishnamachary, B., Zagzag, D., Nagasawa, H., Rainey, K., Okuyama, H., Baek, J. H., & Semenza, G. L. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-3719 · Cited by 415 · see citing works
The biology of hypoxia: the role of oxygen sensing in development, normal function, and disease
Giaccia, A. J., Simon, M. C., & Johnson, R. (2004) · Genes & Development · doi:10.1101/gad.1243304 · Cited by 380 · see citing works
Evaluation of HIF-1 inhibitors as anticancer agents
Semenza, G. L. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2007.08.006 · Cited by 363 · see citing works
Mammalian Per-Arnt-Sim Proteins in Environmental Adaptation
McIntosh, B. E., Hogenesch, J. B., & Bradfield, C. A. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135922 · Cited by 352 · see citing works
A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma
Wallace, E. M., Rizzi, J. P., Han, G., Wehn, P. M., Cao, Z., Du, X., Cheng, T., Czerwinski, R. M., Dixon, D. D., Goggin, B. S., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-0473 · Cited by 336 · see citing works
Multiple Factors Affecting Cellular Redox Status and Energy Metabolism Modulate Hypoxia-Inducible Factor Prolyl Hydroxylase Activity In Vivo and In Vitro
Pan, Y., Mansfield, K. D., Bertozzi, C. C., Rudenko, V., Chan, D. A., Giaccia, A. J., & Simon, M. C. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01223-06 · Cited by 332 · see citing works
Mitochondrial reactive oxygen species regulate hypoxic signaling
Hamanaka, R. B., & Chandel, N. S. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.08.005 · Cited by 332 · see citing works
Mechanisms of hypoxia signalling: new implications for nephrology
Schödel, J., & Ratcliffe, P. J. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0182-z · Cited by 309 · see citing works
Sequence determinants in hypoxia-inducible factor-1α for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3
Huang, J., Zhao, Q., Mooney, S. M., & Lee, F. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206955200 · Cited by 307 · see citing works
Iron-regulatory proteins limit hypoxia-inducible factor-2α expression in iron deficiency
Sanchez, M., Galy, B., Muckenthaler, M. U., & Hentze, M. W. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1222 · Cited by 294 · see citing works
Hypoxia decreases insulin signaling pathways in adipocytes.
Regazzetti, C., Peraldi, P., Grémeaux, T., Najem-Lendom, R., Ben-Sahra, I., Cormont, M., Bost, F., Le Marchand-Brustel, Y., Tanti, J.-F., & Giorgetti-Peraldi, S. (2009) · Diabetes · doi:10.2337/db08-0457 · Cited by 281 · see citing works
Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy
Pringle, K. G., Kind, K. L., Sferruzzi-Perri, A. N., Thompson, J. G., & Roberts, C. T. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmp046 · Cited by 259 · see citing works
A RNA antagonist of hypoxia-inducible factor-1α, EZN-2968, inhibits tumor cell growth
Greenberger, L. M., Horak, I. D., Filpula, D., Sapra, P., Westergaard, M., Frydenlund, H. F., Albæk, C., Schrøder, H., & Ørum, H. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0510 · Cited by 245 · see citing works
Targeting hypoxia-inducible factors: therapeutic opportunities and challenges
Yuan, X., Ruan, W., Bobrow, B., Carmeliet, P., & Eltzschig, H. K. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00848-6 · Cited by 245 · see citing works
Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function
McNamee, E. N., Korns Johnson, D., Homann, D., & Clambey, E. T. (2013) · Immunologic Research · doi:10.1007/s12026-012-8349-8 · Cited by 234 · see citing works
Inhibition of hypoxia-inducible factor 1 activity by nitric oxide donors in hypoxia
Sogawa, K., Numayama-Tsuruta, K., Ema, M., Abe, M., Abe, H., & Fujii-Kuriyama, Y. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7368 · Cited by 224 · see citing works
Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression
Luo, W., Chang, R., Zhong, J., Pandey, A., & Semenza, G. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217394109 · Cited by 228 · see citing works
Role of the hypoxia inducible factors HIF in iron metabolism
Peyssonnaux, C., Nizet, V., & Johnson, R. S. (2008) · Cell Cycle · doi:10.4161/cc.7.1.5145 · Cited by 217 · see citing works
Molecular pathways: hypoxia response in immune cells fighting or promoting cancer
Palazón, A., Aragonés, J., Morales-Kastresana, A., de Landázuri, M. O., & Melero, I. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1591 · Cited by 214 · see citing works
Identification of vascular endothelial growth factor (VEGF) receptor-2 (Flk-1) promoter/enhancer sequences sufficient for angioblast and endothelial cell-specific transcription in transgenic mice
Kappel, A., Rönicke, V., Damert, A., Flamme, I., Risau, W., & Breier, G. (1999) · Blood · doi:10.1182/blood.v93.12.4284 · Cited by 223 · see citing works
The Hypoxia-Inducible Factor 2 α N-Terminal and C-Terminal Transactivation Domains Cooperate To Promote Renal Tumorigenesis In Vivo
Yan, Q., Bartz, S., Mao, M., Li, L., & Kaelin, W. G. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01514-06 · Cited by 193 · see citing works
From oxygen to erythropoietin: Relevance of hypoxia for retinal development, health and disease
Caprara, C., & Grimm, C. (2012) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2011.11.003 · Cited by 176 · see citing works
Hypoxia-inducible factors link iron homeostasis and erythropoiesis
Shah, Y. M., & Xie, L. (2014) · Gastroenterology · doi:10.1053/j.gastro.2013.12.031 · Cited by 187 · see citing works
Redox regulation of the hypoxia-inducible factor
Pouysségur, J., & Mechta-Grigoriou, F. (2006) · Biological Chemistry · doi:10.1515/bc.2006.167 · Cited by 186 · see citing works
EPAS1 trans-activation during hypoxia requires p42/p44 MAPK
Conrad, P. W., Freeman, T. L., Beitner-Johnson, D., & Millhorn, D. E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.47.33709 · Cited by 178 · see citing works
Expression, Ontogeny, and Regulation of Hypoxia-Inducible Transcription Factors in the Human Placenta1
Rajakumar, A., & Conrad, K. P. (2000) · Biology of Reproduction · doi:10.1095/biolreprod63.2.559 · Cited by 177 · see citing works
The HIF pathway and erythrocytosis
Lee, F. S., & Percy, M. J. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130321 · Cited by 177 · see citing works
The Human Hypoxia-Inducible Factor 1α Gene:HIF1AStructure and Evolutionary Conservation
Iyer, N. V., Leung, S. W., & Semenza, G. L. (1998) · Genomics · doi:10.1006/geno.1998.5416 · Cited by 176 · see citing works
Hypoxia-inducible factor-dependent histone deacetylase activity determines stem cell fate in the placenta
Maltepe, E., Krampitz, G. W., Okazaki, K. M., Red-Horse, K., Mak, W., Simon, M. C., & Fisher, S. J. (2005) · Development · doi:10.1242/dev.01923 · Cited by 169 · see citing works
Hypoxia-Inducible Factor Augments Experimental Colitis Through an MIF–Dependent Inflammatory Signaling Cascade
Shah, Y. M., Ito, S., Morimura, K., Chen, C., Yim, S., Haase, V. H., & Gonzalez, F. J. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.009 · Cited by 168 · see citing works
Hypoxia increases sirtuin 1 expression in a hypoxia-inducible factor-dependent manner
Chen, R., Dioum, E. M., Hogg, R. T., Gerard, R. D., & Garcia, J. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.175414 · Cited by 155 · see citing works
Characterization of an Oxygen/Redox-Dependent Degradation Domain of Hypoxia-Inducible Factor α (HIF-α) Proteins
Srinivas, V., Zhang, L.-P., Zhu, X.-H., & Caro, J. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0878 · Cited by 140 · see citing works
The role of hypoxia-inducible factor-2 in digestive system cancers
Zhao, J., Du, F., Shen, G., Zheng, F., & Xu, B. (2015) · Cell Death & Disease · doi:10.1038/cddis.2014.565 · Cited by 122 · see citing works
Hypoxia and the phenomenon of immune exclusion
Pietrobon, V., & Marincola, F. M. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-020-02667-4 · Cited by 119 · see citing works
Hypoxia: Adapting to High Altitude by Mutating EPAS-1 , the Gene Encoding HIF-2α
Tissot van Patot, M. C., & Gassmann, M. (2011) · High Altitude Medicine & Biology · doi:10.1089/ham.2010.1099 · Cited by 119 · see citing works
Implication of the hypoxia response element of the Vegf promoter in mouse models of retinal and choroidal neovascularization, but not retinal vascular development
Vinores, S. A., Xiao, W., Aslam, S., Shen, J., Oshima, Y., Nambu, H., Liu, H., Carmeliet, P., & Campochiaro, P. A. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20525 · Cited by 99 · see citing works
Oxygen Sensing in Retinal Health and Disease
Lange, C. A. K., & Bainbridge, J. W. B. (2012) · Ophthalmologica · doi:10.1159/000331418 · Cited by 86 · see citing works
A protective role for HIF-1 in response to redox manipulation and glucose deprivation: Implications for tumorigenesis
Williams, K. J., Telfer, B. A., Airley, R. E., Peters, H. P., Sheridan, M. R., van der Kogel, A. J., Harris, A. L., & Stratford, I. J. (2002) · Oncogene · doi:10.1038/sj.onc.1205047 · Cited by 81 · see citing works
Identification of Cys255 in HIF‐1α as a novel site for development of covalent inhibitors of HIF‐1α/ARNT PasB domain protein–protein interaction
Cardoso, R., Love, R., Nilsson, C. L., Bergqvist, S., Nowlin, D., Yan, J., Liu, K. K. ‐., Zhu, J., Chen, P., Deng, Y., et al. (2012) · Protein Science · doi:10.1002/pro.2172 · Cited by 79 · see citing works
Deferoxamine induces prolonged cardiac preconditioning via accumulation of oxygen radicals
Dendorfer, A., Heidbreder, M., Hellwig-Bürgel, T., Jöhren, O., Qadri, F., & Dominiak, P. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.10.015 · Cited by 68 · see citing works
Pharmacogenetic Associations with Vascular Endothelial Growth Factor Inhibition in Participants with Neovascular Age-related Macular Degeneration in the IVAN Study
Lotery, A. J., Gibson, J., Cree, A. J., Downes, S. M., Harding, S. P., Rogers, C. A., Reeves, B. C., Ennis, S., & Chakravarthy, U. (2013) · Ophthalmology · doi:10.1016/j.ophtha.2013.07.046 · Cited by 64 · see citing works
Prognostic role of hypoxia-inducible factor-2α tumor cell expression in cancer patients: a meta-analysis
Moreno Roig, E., Yaromina, A., Houben, R., Groot, A. J., Dubois, L., & Vooijs, M. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00224 · Cited by 60 · see citing works
Identification of oleoylethanolamide as an endogenous ligand for HIF-3α
Diao, X., Ye, F., Zhang, M., Ren, X., Tian, X., Lu, J., Sun, X., Hou, Z., Chen, X., Li, F., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30338-z · Cited by 51 · see citing works
The microenvironment for erythropoiesis is regulated by HIF-2α through VCAM-1 in endothelial cells
Yamashita, T., Ohneda, O., Sakiyama, A., Iwata, F., Ohneda, K., & Fujii-Kuriyama, Y. (2008) · Blood · doi:10.1182/blood-2007-11-122648 · Cited by 44 · see citing works
Multifaceted Interplay between Hormones, Growth Factors and Hypoxia in the Tumor Microenvironment
Lappano, R., Todd, L. A., Stanic, M., Cai, Q., Maggiolini, M., Marincola, F., & Pietrobon, V. (2022) · Cancers · doi:10.3390/cancers14030539 · Cited by 32 · see citing works
Bortezomib attenuates HIF-1- but not HIF-2-mediated transcriptional activation
ABD-AZIZ, N., STANBRIDGE, E. J., & SHAFEE, N. (2015) · Oncology Letters · doi:10.3892/ol.2015.3545 · Cited by 31 · see citing works
HIF gene expression in cancer therapy
Chan, D. A., Krieg, A. J., Turcotte, S., & Giaccia, A. J. (2007) · Methods in Enzymology · doi:10.1016/s0076-6879(07)35016-7 · Cited by 26 · see citing works
Hypoxia-inducible factor: roles in development, physiology, and disease
Chandel, N. S., & Simon, M. C. (2008) · Cell Death & Differentiation · doi:10.1038/cdd.2008.11 · Cited by 26 · see citing works
Specific inhibition of HIF activity: can peptides lead the way?
Mylonis, I., Chachami, G., & Simos, G. (2021) · Cancers · doi:10.3390/cancers13030410 · Cited by 21 · see citing works
HIF1α is not a target of 14q deletion in clear cell renal cancer
Shenoy, N. (2020) · Scientific Reports · doi:10.1038/s41598-020-74631-7 · Cited by 14 · see citing works
Neovascularization induced by hypoxia inducible transcription factor is associated with the improvement of cardiac dysfunction in experimental autoimmune myocarditis
Tada, Y., Ogawa, M., Watanabe, R., Zempo, H., Takamura, C., Suzuki, J.-I., Dan, T., Miyata, T., Isobe, M., & Komuro, I. (2014) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2014.855196 · Cited by 9 · see citing works

Authors: Tian, H., McKnight, S. L., & Russell, D. W.
Affiliations: The University of Texas Southwestern Medical Center (US)
ORCID: McKnight, S L
Russell, D W
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 1997-01-01
Volume: 11
Issue: 1
Pages: 72-82
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.11.1.72
OpenAlex: W2102476325
Cited by: 1,351
References: 5
Citations by year: 2026: 25 · 2025: 13 · 2024: 29 · 2023: 44 · 2022: 39 · 2021: 45 · 2020: 60 · 2019: 43 · 2018: 41 · 2017: 38 · 2016: 51 · 2015: 49 · 2014: 44 · 2013: 53 · 2012: 64
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5p50dk047657-10, 5r01ca052121-07)
National Cancer Institute (CA52121)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 47657)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
Keywords: EPAS1, hypoxia-inducible factor-1α, HIF-1α, erythropoietin gene, transcriptional activation, heterodimeric complex, Tie2, endothelial cells, hypoxia, vascularization, endothelial cell gene expression
MeSH terms: Amino Acid Sequence, Cloning, Molecular, DNA-Binding Proteins, HeLa Cells, Humans, Molecular Sequence Data, Nuclear Proteins, RNA, Transcription Factors, Transfection, Blotting, Northern, Transcriptional Activation, Sequence Alignment, In Situ Hybridization, Sequence Analysis, Genes, Reporter, Helix-Loop-Helix Motifs, Receptors, Aryl Hydrocarbon, Dimerization, Aryl Hydrocarbon Receptor Nuclear Translocator, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit

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

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