A distinct class of antioxidant response elements is consistently activated in tumors with NRF2 mutations

Sykiotis, 2010, Stress-activated cap'n'collar transcription factors in aging and human disease, Sci. Signal., 3, re3, 10.1126/scisignal.3112re3 Holmstrom, 2014, Cellular mechanisms and physiological consequences of redox-dependent signalling, Nat. Rev. Mol. Cell Biol., 15, 411, 10.1038/nrm3801 Waris, 2006, Reactive oxygen species: role in the development of cancer and various chronic conditions, J. Carcinog., 5, 14, 10.1186/1477-3163-5-14 Barja, 2004, Free radicals and aging, Trends Neurosci., 27, 595, 10.1016/j.tins.2004.07.005 Jimenez-Del-Rio, 2012, The bad, the good, and the ugly about oxidative stress, Oxid. Med. Cell. Longev., 2012, 163913, 10.1155/2012/163913 Halliwell, 2007, Biochemistry of oxidative stress, Biochem. Soc. Trans., 35, 1147, 10.1042/BST0351147 Leinonen, 2015, Dysregulation of the Keap1-Nrf2 pathway in cancer, Biochem. Soc. Trans., 43, 645, 10.1042/BST20150048 Zhang, 2015, Oxidative stress response and Nrf2 signaling in aging, Free Radic. Biol. Med., 10.1016/j.freeradbiomed.2015.05.036 Suzuki, 2017, Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2 system during cellular stress, J. Biol. Chem., 292, 16817, 10.1074/jbc.R117.800169 Friling, 1990, Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by an electrophile-responsive element, Proc. Natl. Acad. Sci. USA, 87, 6258, 10.1073/pnas.87.16.6258 Otsuki, 2016, Unique cistrome defined as CsMBE is strictly required for Nrf2-sMaf heterodimer function in cytoprotection, Free Radic. Biol. Med., 91, 45, 10.1016/j.freeradbiomed.2015.12.005 Rushmore, 1991, The antioxidant responsive element. activation by oxidative stress and identification of the DNA consensus sequence required for functional activity, J. Biol. Chem., 266, 11632, 10.1016/S0021-9258(18)99004-6 Itoh, 1997, An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements, Biochem. Biophys. Res. Commun., 236, 313, 10.1006/bbrc.1997.6943 Kannan, 2012, The small MAF transcription factors MAFF, MAFG and MAFK: current knowledge and perspectives, Biochim. Et. Biophys. Acta, 1823, 1841, 10.1016/j.bbamcr.2012.06.012 Toki, 1997, Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif, Oncogene, 14, 1901, 10.1038/sj.onc.1201024 Zipper, 2002, The Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm, J. Biol. Chem., 277, 36544, 10.1074/jbc.M206530200 Wakabayashi, 2003, Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation, Nat. Genet., 35, 238, 10.1038/ng1248 McMahon, 2003, Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression, J. Biol. Chem., 278, 21592, 10.1074/jbc.M300931200 Itoh, 1999, Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain, Genes Dev., 13, 76, 10.1101/gad.13.1.76 Kansanen, 2013, The Keap1-Nrf2 pathway: mechanisms of activation and dysregulation in cancer, Redox Biol., 1, 45, 10.1016/j.redox.2012.10.001 Dinkova-Kostova, 2002, Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants, Proc. Natl. Acad. Sci. USA, 99, 11908, 10.1073/pnas.172398899 Malhotra, 2010, Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis, Nucleic Acids Res., 38, 5718, 10.1093/nar/gkq212 Chorley, 2012, Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha, Nucleic Acids Res., 40, 7416, 10.1093/nar/gks409 Lacher, 2015, Beyond antioxidant genes in the ancient Nrf2 regulatory network, Free Radic. Biol. Med., 88, 452, 10.1016/j.freeradbiomed.2015.06.044 Hayes, 2014, The Nrf2 regulatory network provides an interface between redox and intermediary metabolism, Trends Biochem. Sci., 39, 199, 10.1016/j.tibs.2014.02.002 Lee, 2007, An auto-regulatory loop between stress sensors INrf2 and Nrf2 controls their cellular abundance, J. Biol. Chem., 282, 36412, 10.1074/jbc.M706517200 Sykiotis, 2008, Keap1/Nrf2 signaling regulates oxidative stress tolerance and lifespan in Drosophila, Dev. Cell, 14, 76, 10.1016/j.devcel.2007.12.002 Oh, 2012, Deficiency in the nuclear-related factor erythroid 2 transcription factor (Nrf1) leads to genetic instability, FEBS J., 279, 4121, 10.1111/febs.12005 Gan, 2014, Oxidative damage and the Nrf2-ARE pathway in neurodegenerative diseases, Biochim. Et. Biophys. Acta, 1842, 1208, 10.1016/j.bbadis.2013.12.011 Singh, 2006, Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer, PLoS Med., 3, e420, 10.1371/journal.pmed.0030420 Shibata, 2008, Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy, Proc. Natl. Acad. Sci. USA, 105, 13568, 10.1073/pnas.0806268105 Konstantinopoulos, 2011, Keap1 mutations and Nrf2 pathway activation in epithelial ovarian cancer, Cancer Res., 71, 5081, 10.1158/0008-5472.CAN-10-4668 Kim, 2010, Oncogenic NRF2 mutations in squamous cell carcinomas of oesophagus and skin, J. Pathol., 220, 446, 10.1002/path.2653 Cancer Genome Atlas Research, 2012, Comprehensive genomic characterization of squamous cell lung cancers, Nature, 489, 519, 10.1038/nature11404 Padmanabhan, 2006, Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer, Mol. Cell, 21, 689, 10.1016/j.molcel.2006.01.013 Ganan-Gomez, 2013, Oncogenic functions of the transcription factor Nrf2, Free Radic. Biol. Med., 65, 750, 10.1016/j.freeradbiomed.2013.06.041 Menegon, 2016, The Dual Roles of NRF2 in Cancer, Trends Mol. Med., 22, 578, 10.1016/j.molmed.2016.05.002 Cancer Genome Atlas, 2015, Comprehensive genomic characterization of head and neck squamous cell carcinomas, Nature, 517, 576, 10.1038/nature14129 Gibson, 2016, The genomic landscape and evolution of endometrial carcinoma progression and abdominopelvic metastasis, Nat. Genet., 48, 848, 10.1038/ng.3602 Wang, 2015, Hypermethylation of the Keap1 gene inactivates its function, promotes Nrf2 nuclear accumulation, and is involved in arsenite-induced human keratinocyte transformation, Free Radic. Biol. Med., 89, 209, 10.1016/j.freeradbiomed.2015.07.153 Martinez, 2013, Frequent concerted genetic mechanisms disrupt multiple components of the NRF2 inhibitor KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex in thyroid cancer, Mol. Cancer, 12, 124, 10.1186/1476-4598-12-124 Martinez, 2015, Disruption of KEAP1/CUL3/RBX1 E3-ubiquitin ligase complex components by multiple genetic mechanisms: Association with poor prognosis in head and neck cancer, Head. neck, 37, 727, 10.1002/hed.23663 Zhang, 2010, Loss of Kelch-like ECH-associated protein 1 function in prostate cancer cells causes chemoresistance and radioresistance and promotes tumor growth, Mol. Cancer Ther., 9, 336, 10.1158/1535-7163.MCT-09-0589 Wang, 2008, Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues, Biochem. Biophys. Res. Commun., 373, 151, 10.1016/j.bbrc.2008.06.004 DeNicola, 2011, Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis, Nature, 475, 106, 10.1038/nature10189 Komatsu, 2010, The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1, Nat. Cell Biol., 12, 213, 10.1038/ncb2021 Papp, 2012, The NRF2-related interactome and regulome contain multifunctional proteins and fine-tuned autoregulatory loops, FEBS Lett., 586, 1795, 10.1016/j.febslet.2012.05.016 Turei, 2013, NRF2-ome: an integrated web resource to discover protein interaction and regulatory networks of NRF2, Oxid. Med. Cell. Longev., 2013, 737591, 10.1155/2013/737591 Wardyn, 2015, Dissecting molecular cross-talk between Nrf2 and NF-kappaB response pathways, Biochem. Soc. Trans., 43, 621, 10.1042/BST20150014 Alam, 2017, Glucocorticoid receptor signaling represses the antioxidant response by inhibiting histone acetylation mediated by the transcriptional activator NRF2, J. Biol. Chem., 292, 7519, 10.1074/jbc.M116.773960 Cuadrado, 2018, Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach, Pharmacol. Rev., 70, 348, 10.1124/pr.117.014753 Gonzalez-Perez, 2013, IntOGen-mutations identifies cancer drivers across tumor types, Nat. Methods, 10, 1081, 10.1038/nmeth.2642 Mitsuishi, 2012, Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming, Cancer Cell, 22, 66, 10.1016/j.ccr.2012.05.016 Chartoumpekis, 2015, Keap1/Nrf2 pathway in the frontiers of cancer and non-cancer cell metabolism, Biochem. Soc. Trans., 43, 639, 10.1042/BST20150049 Murakami, 2015, Roles of Nrf2 in cell proliferation and differentiation, Free Radic. Biol. Med., 88, 168, 10.1016/j.freeradbiomed.2015.06.030 Chio, 2016, NRF2 promotes tumor maintenance by modulating mrna translation in pancreatic cancer, 166, 963 Kitamura, 2018, NRF2 addiction in cancer cells, Cancer Sci., 109, 900, 10.1111/cas.13537 Lacher, 2016, Gene regulatory effects of disease-associated variation in the NRF2 network, Curr. Opin. Toxicol., 1, 71, 10.1016/j.cotox.2016.09.001 Peng, 2016, Suppression of NRF2-ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells, Toxicology Appl. Pharmacol., 292, 1, 10.1016/j.taap.2015.12.008 Zhan, 2012, Regulatory role of KEAP1 and NRF2 in PPARgamma expression and chemoresistance in human non-small-cell lung carcinoma cells, Free Radic. Biol. Med., 53, 758, 10.1016/j.freeradbiomed.2012.05.041 Zhu, 2016, An overview of chemical inhibitors of the Nrf2-ARE signaling pathway and their potential applications in cancer therapy, Free Radic. Biol. Med., 99, 544, 10.1016/j.freeradbiomed.2016.09.010 Araya, 2016, Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations, Nat. Genet., 48, 117, 10.1038/ng.3471 Wang, 2016, A polymorphic antioxidant response element links NRF2/sMAF binding to Enhanced MAPT expression and reduced risk of parkinsonian disorders, Cell Rep. Hur, 2011, Small molecule modulators of antioxidant response pathway, Curr. Opin. Chem. Biol., 15, 162, 10.1016/j.cbpa.2010.12.009 Chen, 2013, Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool, BMC Bioinforma., 14, 128, 10.1186/1471-2105-14-128 Kuleshov, 2016, Enrichr: a comprehensive gene set enrichment analysis web server 2016 update, Nucleic Acids Res., 44, 10.1093/nar/gkw377 Lynch, 2009, Cell survival under stress is enhanced by a mitochondrial ATP-binding cassette transporter that regulates hemoproteins, Cancer Res., 69, 5560, 10.1158/0008-5472.CAN-09-0078 Schaedler, 2015, Structures and functions of mitochondrial ABC transporters, Biochem. Soc. Trans., 43, 943, 10.1042/BST20150118 Yu, 2014, Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway, Cancer Lett., 353, 182, 10.1016/j.canlet.2014.07.025 Canet, 2015, Identification of a functional antioxidant response element within the eighth intron of the human ABCC3 gene, Drug Metab. Dispos.: Biol. fate Chem., 43, 93, 10.1124/dmd.114.060103 Hong, 2016, NAMPT suppresses glucose deprivation-induced oxidative stress by increasing NADPH levels in breast cancer, Oncogene, 35, 3544, 10.1038/onc.2015.415 Cerna, 2012, Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) activity by small molecule GMX1778 regulates reactive oxygen species (ROS)-mediated cytotoxicity in a p53- and nicotinic acidphosphoribosyltransferase1 (NAPRT1)-dependent manner, J. Biol. Chem., 287, 22408, 10.1074/jbc.M112.357301 Moore, 2015, NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective, PAR-independent metabolic catastrophe and cell death induced by beta-lapachone, Cell Death Dis., 6, e1599, 10.1038/cddis.2014.564 Xu, 2016, Transketolase counteracts oxidative stress to drive cancer development, Proc. Natl. Acad. Sci. USA, 113, E725, 10.1073/pnas.1508779113 Szklarczyk, 2017, The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible, Nucleic Acids Res., 45, D362, 10.1093/nar/gkw937 Piazza, 2017, OncoScore: a novel, Internet-based tool to assess the oncogenic potential of genes, Sci. Rep., 7, 46290, 10.1038/srep46290 Futreal, 2004, A census of human cancer genes, Nat. Rev. Cancer, 4, 177, 10.1038/nrc1299 Fisher, 2012, DNA regions bound at low occupancy by transcription factors do not drive patterned reporter gene expression in Drosophila, Proc. Natl. Acad. Sci. USA, 109, 21330, 10.1073/pnas.1209589110 Slattery, 2014, Absence of a simple code: how transcription factors read the genome, Trends Biochem. Sci., 39, 381, 10.1016/j.tibs.2014.07.002 Li, 2011, The role of chromatin accessibility in directing the widespread, overlapping patterns of Drosophila transcription factor binding, Genome Biol., 12, R34, 10.1186/gb-2011-12-4-r34 Ernst, 2013, Interplay between chromatin state, regulator binding, and regulatory motifs in six human cell types, Genome Res., 23, 1142, 10.1101/gr.144840.112 Slattery, 2013, Divergent transcriptional regulatory logic at the intersection of tissue growth and developmental patterning, PLoS Genet., 9, e1003753, 10.1371/journal.pgen.1003753 Xin, 2018, Relationship between histone modifications and transcription factor binding is protein family specific, Genome Res., 10.1101/gr.220079.116 Sabo, 2006, Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays, Nat. Methods, 3, 511, 10.1038/nmeth890 Thurman, 2012, The accessible chromatin landscape of the human genome, Nature, 489, 75, 10.1038/nature11232 Chung, 2011, Discovering transcription factor binding sites in highly repetitive regions of genomes with multi-read analysis of ChIP-Seq data, PLoS Comput. Biol., 7, e1002111, 10.1371/journal.pcbi.1002111 Afek, 2015, Nonconsensus protein binding to repetitive DNA sequence elements significantly affects eukaryotic genomes, PLoS Comput. Biol., 11, e1004429, 10.1371/journal.pcbi.1004429 Deininger, 2011, Alu elements: know the SINEs, Genome Biol., 12, 236, 10.1186/gb-2011-12-12-236 Kundaje, 2015, Integrative analysis of 111 reference human epigenomes, Nature, 518, 317, 10.1038/nature14248 Layer, 2018, GIGGLE: a search engine for large-scale integrated genome analysis, Nat. Methods, 15, 123, 10.1038/nmeth.4556 Pekowska, 2011, H3K4 tri-methylation provides an epigenetic signature of active enhancers, EMBO J., 30, 4198, 10.1038/emboj.2011.295 Core, 2014, Analysis of nascent RNA identifies a unified architecture of initiation regions at mammalian promoters and enhancers, Nat. Genet., 46, 1311, 10.1038/ng.3142 Andersson, 2015, A unified architecture of transcriptional regulatory elements, Trends Genet.: TIG, 31, 426, 10.1016/j.tig.2015.05.007 Wang, 2017, High-resolution genome-wide functional dissection of transcriptional regulatory regions in human, bioRxiv, 193136 Darnell, 2002, Transcription factors as targets for cancer therapy, Nat. Rev. Cancer, 2, 740, 10.1038/nrc906 Bhagwat, 2015, Targeting transcription factors in cancer, Trends Cancer, 1, 53, 10.1016/j.trecan.2015.07.001 Bradner, 2017, Transcriptional Addiction in Cancer, Cell, 168, 629, 10.1016/j.cell.2016.12.013 Cancer Genome Atlas Research, 2013, Integrated genomic characterization of endometrial carcinoma, Nature, 497, 67, 10.1038/nature12113 Cancer Genome Atlas Research, 2014, Comprehensive molecular characterization of urothelial bladder carcinoma, Nature, 507, 315, 10.1038/nature12965 Cancer Genome Atlas Research, 2014, Comprehensive molecular profiling of lung adenocarcinoma, Nature, 511, 543, 10.1038/nature13385 Chapple, 2016, Bach1 differentially regulates distinct Nrf2-dependent genes in human venous and coronary artery endothelial cells adapted to physiological oxygen levels, Free Radic. Biol. Med., 92, 152, 10.1016/j.freeradbiomed.2015.12.013 Fang, 2014, The BRAF oncoprotein functions through the transcriptional repressor MAFG to mediate the CpG Island Methylator phenotype, Mol. Cell, 55, 904, 10.1016/j.molcel.2014.08.010 Kobayashi, 2004, Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2, Mol. Cell. Biol., 24, 7130, 10.1128/MCB.24.16.7130-7139.2004 Cullinan, 2004, The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase, Mol. Cell. Biol., 24, 8477, 10.1128/MCB.24.19.8477-8486.2004 Zhang, 2004, Keap1 is a redox-regulated substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex, Mol. Cell. Biol., 24, 10941, 10.1128/MCB.24.24.10941-10953.2004 Ooi, 2013, CUL3 and NRF2 mutations confer an NRF2 activation phenotype in a sporadic form of papillary renal cell carcinoma, Cancer Res., 73, 2044, 10.1158/0008-5472.CAN-12-3227 Sosa, 2013, Oxidative stress and cancer: an overview, Ageing Res. Rev., 12, 376, 10.1016/j.arr.2012.10.004 Forman, 2014, How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo, Free Radic. Biol. Med., 66, 24, 10.1016/j.freeradbiomed.2013.05.045 Harris, 2015, Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression, Cancer Cell, 10.1016/j.ccell.2015.01.009 Tseng, 2018, Transketolase regulates the metabolic switch to control breast cancer cell metastasis via the alpha-ketoglutarate signaling pathway, Cancer Res., 10.1158/0008-5472.CAN-17-2906 Lu, 2018, ME1 regulates NADPH homeostasis to promote gastric cancer growth and metastasis, Cancer Res., 78, 1972, 10.1158/0008-5472.CAN-17-3155 Murai, 2017, Inhibition of malic enzyme 1 disrupts cellular metabolism and leads to vulnerability in cancer cells in glucose-restricted conditions, Oncogenesis, 6, e329, 10.1038/oncsis.2017.34 Townsend, 2003, The role of glutathione-S-transferase in anti-cancer drug resistance, Oncogene, 22, 7369, 10.1038/sj.onc.1206940 Decker, 2009, Mammalian epoxide hydrolases in xenobiotic metabolism and signalling, Arch. Toxicol., 83, 297, 10.1007/s00204-009-0416-0 Minami, 2014, Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine, Anticancer Res., 34, 4767 Xiong, 2014, Elevated expression of AKR1C3 increases resistance of cancer cells to ionizing radiation via modulation of oxidative stress, PloS One, 9, e111911, 10.1371/journal.pone.0111911 Fiorillo, 2017, Mitochondrial "power" drives tamoxifen resistance: NQO1 and GCLC are new therapeutic targets in breast cancer, Oncotarget, 8, 20309, 10.18632/oncotarget.15852 Aeby, 2016, Peroxiredoxin 1 protects telomeres from oxidative damage and preserves telomeric DNA for extension by telomerase, Cell Rep., 17, 3107, 10.1016/j.celrep.2016.11.071 Sillje, 2001, Identification of human Asf1 chromatin assembly factors as substrates of Tousled-like kinases, Curr. Biol.: CB, 11, 1068, 10.1016/S0960-9822(01)00298-6 Mello, 2002, Human Asf1 and CAF-1 interact and synergize in a repair-coupled nucleosome assembly pathway, EMBO Rep., 3, 329, 10.1093/embo-reports/kvf068 Sen, 2006, TLK1B promotes repair of UV-damaged DNA through chromatin remodeling by Asf1, BMC Mol. Biol., 7, 37, 10.1186/1471-2199-7-37 Klimovskaia, 2014, Tousled-like kinases phosphorylate Asf1 to promote histone supply during DNA replication, Nat. Commun., 5, 3394, 10.1038/ncomms4394 Team, 2017 Wickham, 2017, readxl: Read. Excel Files. Chen, 2016, VennDiagram: generate high‐resolution Venn Euler plots Wang, 2007, Identification of polymorphic antioxidant response elements in the human genome, Human. Mol. Genet., 16, 1188, 10.1093/hmg/ddm066 Consortium, 2012, An integrated encyclopedia of DNA elements in the human genome, Nature, 489, 57, 10.1038/nature11247 Quinlan, 2010, BEDTools: a flexible suite of utilities for comparing genomic features, Bioinformatics, 26, 841, 10.1093/bioinformatics/btq033 Mermel, 2011, GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancers, Genome Biol., 12, R41, 10.1186/gb-2011-12-4-r41 R. Kolde, Pheatmap: Pretty heatmaps. 2015. Ramskold, 2009, An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data, PLoS Comput. Biol., 5, e1000598, 10.1371/journal.pcbi.1000598