The DOI matches its Crossref record; 45 of the 46 references it cites were found in a registry or an index.
Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Open accessAbstract
Transcription factor Nrf2 is essential for the antioxidant responsive element (ARE)-mediated induction of phase II detoxifying and oxidative stress enzyme genes. Detailed analysis of differential Nrf2 activity displayed in transfected cell lines ultimately led to the identification of a new protein, which we named Keap1, that suppresses Nrf2 transcriptional activity by specific binding to its evolutionarily conserved amino-terminal regulatory domain. The closest homolog of Keap1 is a Drosophila actin-binding protein called Kelch, implying that Keap1 might be a Nrf2 cytoplasmic effector. We then showed that electrophilic agents antagonize Keap1 inhibition of Nrf2 activity in vivo, allowing Nrf2 to traverse from the cytoplasm to the nucleus and potentiate the ARE response. We postulate that Keap1 and Nrf2 constitute a crucial cellular sensor for oxidative stress, and together mediate a key step in the signaling pathway that leads to transcriptional activation by this novel Nrf2 nuclear shuttling mechanism. The activation of Nrf2 leads in turn to the induction of phase II enzyme and antioxidative stress genes in response to electrophiles and reactive oxygen species.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The N-terminal Neh2 domain is a redox-sensitive degron that negatively regulates Nrf2 activity and contains two highly conserved 29DLG31 and 79ETGE82 motifs to which Keap1 binds, as well as seven lysine residues that are targets for ubiquitination by the Cul3 E3 ubiquitin ligase [49,65].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [49]
In the citing paper
“Nrf2 regulates the expression of a multitude of antioxidant and phase II enzyme genes and is negatively regulated by Kelch-like ECH-associated protein (Keap1) [49], a substrate adaptor protein that binds to Nrf2 in the cytosol to facilitate its polyubiquitination by the Cullin 3 (Cul3) E3 ubiquitin ligase for proteasomal degradation [50,51,52].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [49]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589
Ashburner, M. (1989) · Cold Spring Harbor Laboratory eBooks · Cited by 6,756
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6943 · Cited by 3,999
Hayes, J. D., & Pulford, D. J. (1995) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409239509083491 · Cited by 3,464
Dietary Carcinogens and Anticarcinogens
Ames, B. N. (1983) · Science · doi:10.1126/science.6351251 · Cited by 2,975
Moi, P., Chan, K., Asunis, I., Cao, A., & Kan, Y. W. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9926 · Cited by 1,607
pEF-BOS, a powerful mammalian expression vector
Mizushima, S., & Nagata, S. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.17.5322 · Cited by 1,594
Rushmore, T. H., Morton, M. R., & Pickett, C. B. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99004-6 · Cited by 1,464
Carcinogenesis by chemicals: an overview--G. H. A. Clowes memorial lecture.
MILLER, J. A. (1970) · PubMed · Cited by 1,453
Metabolic activation of benzo(a)pyrene proceeds by a diol-epoxide
Sims, P. H., Grover, P. L., Swaisland, A. J., Pal, K., & Hewer, A. J. (1974) · Nature · doi:10.1038/252326a0 · Cited by 1,134
Flagged first, then by citations
1 of the 46 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 401–500 of 1,018
Nrf2: A Potential Target for New Therapeutics in Liver Disease
Bataille, A. M., & Manautou, J. E. (2012) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2012.110 · Cited by 230
Apopa, P. L., He, X., & Ma, Q. (2008) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.20212 · Cited by 230
Pi, J., Qu, W., Reece, J. M., Kumagai, Y., & Waalkes, M. P. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00341-0 · Cited by 231
Structural assembly of cullin-RING ubiquitin ligase complexes
Zimmerman, E. S., Schulman, B. A., & Zheng, N. (2010) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2010.08.010 · Cited by 227
Lee, J., Hanson, J. M., Chu, W. A., & Johnson, J. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100734200 · Cited by 229
Redox signaling in cardiovascular health and disease
Madamanchi, N. R., & Runge, M. S. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.04.001 · Cited by 227
Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism
Huang, J., Tabbi‐Anneni, I., Gunda, V., & Wang, L. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00322.2010 · Cited by 228
Antioxidant and anti-proliferative properties of lycopene
Kelkel, M., Schumacher, M. M., Dicato, M. A., & Diederich, M. F. (2011) · Free Radical Research · doi:10.3109/10715762.2011.564168 · Cited by 227
Nrf2/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS
Petri, S., Körner, S., & Kiaei, M. (2012) · Neurology Research International · doi:10.1155/2012/878030 · Cited by 227
Hosoya, T., Maruyama, A., Kang, M.-I., Kawatani, Y., Shibata, T., Uchida, K., Itoh, K., & Yamamoto, M. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502551200 · Cited by 225
Self-citationGenetic Analysis of Cytoprotective Functions Supported by Graded Expression of Keap1
Taguchi, K., Maher, J. M., Suzuki, T., Kawatani, Y., Motohashi, H., & Yamamoto, M. P. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01591-09 · Cited by 225
Self-citationMolecular and Chemical Regulation of the Keap1-Nrf2 Signaling Pathway
Keum, Y., & Choi, B. Y. (2014) · Molecules · doi:10.3390/molecules190710074 · Cited by 225
Osburn, W. O., Wakabayashi, N., Misra, V., Nilles, T. L., Biswal, S. S., Trush, M. A., & Kensler, T. W. (2006) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2006.08.005 · Cited by 225
Self-citationReactive Oxygen Production Induced by the Gut Microbiota: Pharmacotherapeutic Implications
Jones, R. M., Mercante, J. W., & Neish, A. S. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712799828283 · Cited by 232
Fujita, K.-I., Maeda, D., Xiao, Q., & Srinivasula, S. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1014156108 · Cited by 232
Grape Phytochemicals and Associated Health Benefits
Yang, J., & Xiao, Y. (2013) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2012.692408 · Cited by 221
Kim, J.-E., You, D., Lee, C., Ahn, C., Seong, J. Y., & Hwang, J. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.06.004 · Cited by 234
Marchev, A. S., Dimitrova, P. A., Burns, A. J., Kostov, R. V., Dinkova‐Kostova, A. T., & Georgiev, M. I. (2017) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13407 · Cited by 225
Modulation of proteostasis by transcription factor NRF2 and impact in neurodegenerative diseases
Pajares, M., Cuadrado, A., & Rojo, A. I. (2017) · Redox Biology · doi:10.1016/j.redox.2017.01.006 · Cited by 226
Ryoo, I.-G., & Kwak, M. (2018) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2018.09.014 · Cited by 230
Dinkova‐Kostova, A. T., Holtzclaw, W. D., & Wakabayashi, N. (2005) · Biochemistry · doi:10.1021/bi047434h · Cited by 220
Self-citationHu, R., Hebbar, V., Kim, B.-R., Chen, C., Winnik, B., Buckley, B., Soteropoulos, P., Tolias, P. P., Hart, R. P., & Kong, A.-N. T. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.064261 · Cited by 220
Heme Oxgenase-1, a Cardinal Modulator of Regulated Cell Death and Inflammation
Ryter, S. W. (2021) · Cells · doi:10.3390/cells10030515 · Cited by 228
Ma, Q., Kinneer, K., Bi, Y., Chan, J. Y., & Kan, Y. W. (2004) · Biochemical Journal · doi:10.1042/bj20031123 · Cited by 220
Impaired Nuclear Nrf2 Translocation Undermines the Oxidative Stress Response in Friedreich Ataxia
Paupe, V., Dassa, E. P., Gonçalves, S., Auchère, F., Lönn, M. E., Holmgren, A., & Rustin, P. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004253 · Cited by 218
Curcumin Activates the Nrf2 Pathway and Induces Cellular Protection Against Oxidative Injury
Ashrafizadeh, M., Ahmadi, Z., Mohammadinejad, R., Farkhondeh, T., & Samarghandian, S. (2019) · Current Molecular Medicine · doi:10.2174/1566524019666191016150757 · Cited by 218
Li, N., Venkatesan, M. I., Miguel, A., Kaplan, R., Gujuluva, C., Alam, J., & Nel, A. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.165.6.3393 · Cited by 267
Adaptation to Oxidative Stress, Chemoresistance, and Cell Survival
Landriscina, M., Maddalena, F., Laudiero, G., & Esposito, F. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2692 · Cited by 219
Chapple, S. J., Siow, R. C. M., & Mann, G. E. (2012) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2012.04.021 · Cited by 218
Bellezza, I., Tucci, A., Galli, F., Grottelli, S., Mierla, A. L., Pilolli, F., & Minelli, A. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.10.012 · Cited by 216
Gao, X., & Talalay, P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403886101 · Cited by 215
The Role of Reactive Oxygen Species in Regulating T Cell-mediated Immunity and Disease
Yarosz, E. L., & Chang, C.-H. (2018) · Immune Network · doi:10.4110/in.2018.18.e14 · Cited by 214
Nrf2 as a regulator of mitochondrial function: Energy metabolism and beyond
Esteras, N., & Abramov, A. Y. (2022) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2022.07.013 · Cited by 225
Translational strategies for cancer prevention in liver
Kensler, T. W., Qian, G.-S., Chen, J., & Groopman, J. D. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1076 · Cited by 213
Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury
Shah, Z. A., Li, R.-C., Thimmulappa, R. K., Kensler, T. W., Yamamoto, M. P., Biswal, S. S., & Doré, S. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2007.02.066 · Cited by 214
Self-citationNox enzymes as novel targets for drug development
Lambeth, J. D., Krause, K.-H., & Clark, R. A. (2008) · Seminars in Immunopathology · doi:10.1007/s00281-008-0123-6 · Cited by 212
A mutation of Keap1 found in breast cancer impairs its ability to repress Nrf2 activity
Nioi, P., & Nguyen, T. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.08.051 · Cited by 212
BRG1 Interacts with Nrf2 To Selectively Mediate HO-1 Induction in Response to Oxidative Stress
Zhang, J., Ohta, T., Maruyama, A., Hosoya, T., Nishikawa, K., Maher, J. M., Shibahara, S., Itoh, K., & Yamamoto, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00700-06 · Cited by 213
Self-citationMolecular cross-talk between the NRF2/KEAP1 signaling pathway, autophagy, and apoptosis
Stępkowski, T. M., & Kruszewski, M. K. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.01.033 · Cited by 215
Katoh, Y., Iida, K., Kang, M.-I., Kobayashi, A., Mizukami, M., Tong, K. I., McMahon, M. J., Hayes, J. D., Itoh, K., & Yamamoto, M. P. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.10.012 · Cited by 217
Self-citationInvolvement of Cytochrome P450 in Reactive Oxygen Species Formation and Cancer
Hrycay, E. G., & Bandiera, S. M. (2015) · Advances in pharmacology · doi:10.1016/bs.apha.2015.03.003 · Cited by 234
Bahn, G., Park, J.-S., Yun, U. J., Lee, Y. J., Choi, Y., Park, J. S., Baek, S. H., Choi, B. Y., Cho, Y. S., Kim, H. K., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1819541116 · Cited by 210
Self-citationNezu, M., Souma, T., Yu, L., Suzuki, T., Saigusa, D., Ito, S., Suzuki, N., & Yamamoto, M. P. (2016) · Kidney International · doi:10.1016/j.kint.2016.08.023 · Cited by 211
Self-citationHannan, M. A., Dash, R., Sohag, A. A. M., Haque, M. N., & Moon, I. S. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00116 · Cited by 215
Vollenweider, S., Weber, H. H., Stolz, S., Chételat, A., & Farmer, E. E. (2000) · The Plant Journal · doi:10.1046/j.1365-313x.2000.00897.x · Cited by 211
Rachakonda, G., Xiong, Y., Sekhar, K. R., Stamer, S. L., Liebler, D. C., & Freeman, M. L. (2008) · Chemical Research in Toxicology · doi:10.1021/tx700302s · Cited by 210
Free radical biology and medicine
(2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00493-3 · Cited by 209
Activation of stress signaling pathways by electrophilic oxidized and nitrated lipids
Kansanen, E., Jyrkkänen, H.-K., & Levonen, A. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.11.038 · Cited by 210
Cao, J. Y., Poddar, A., Magtanong, L., Lumb, J. H., Mileur, T. R., Reid, M. A., Dovey, C. M., Wang, J., Locasale, J. W., Stone, E. M., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.043 · Cited by 212
Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice
Goldring, C. E., Kitteringham, N. R., Elsby, R., Randle, L. E., Clement, Y. N., Williams, D. P., McMahon, M. J., Hayes, J. D., Itoh, K., Yamamoto, M. P., et al. (2004) · Hepatology · doi:10.1002/hep.20183 · Cited by 207
Self-citationSakurai, A., Nishimoto, M., Himeno, S., Imura, N., Tsujimoto, M., Kunimoto, M., & Hara, S. (2004) · Journal of Cellular Physiology · doi:10.1002/jcp.20246 · Cited by 210
Dietz, B. M., Kang, Y., Liu, G., Eggler, A. L., Yao, P., Chadwick, L. R., Pauli, G. F., Farnsworth, N. R., Mesecar, A. D., van Breemen, R. B., et al. (2005) · Chemical Research in Toxicology · doi:10.1021/tx050058x · Cited by 207
Walters, D. M., Cho, H., & Kleeberger, S. R. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1901 · Cited by 205
Saha, S., Buttari, B., Profumo, E., Tucci, P., & Saso, L. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.787258 · Cited by 185
Heme Oxygenase and Atherosclerosis
Morita, T. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000178169.95781.49 · Cited by 206
An Auto-regulatory Loop between Stress Sensors INrf2 and Nrf2 Controls Their Cellular Abundance
Lee, O.-H., Jain, A. K., Papusha, V. Z., & Jaiswal, A. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706517200 · Cited by 205
Nrf2 Protects Pancreatic β-Cells From Oxidative and Nitrosative Stress in Diabetic Model Mice
Yagishita, Y., Fukutomi, T., Sugawara, A., Kawamura, H., Takahashi, T., Pi, J., Uruno, A., & Yamamoto, M. P. (2013) · Diabetes · doi:10.2337/db13-0909 · Cited by 205
Self-citationMolecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease
Cioffi, F., Adam, R. H. I., & Broersen, K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190863 · Cited by 204
“652 In the absence of oxidative stress, Nrf2 is transcrip653 tionally inactive as its activity is repressed by Keap1 654 [154].”
BackgroundKEAP1–NRF2 signalling and autophagy in protection against oxidative and reductive proteotoxicity
Dodson, M. B., Redmann, M., Rajasekaran, N. S., Darley-Usmar, V. M., & Zhang, J. (2015) · Biochemical Journal · doi:10.1042/bj20150568 · Cited by 204
Oncogenic potential of Nrf2 and its principal target protein heme oxygenase-1
Na, H., & Surh, Y. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.10.819 · Cited by 203
The Role of Nrf2-Mediated Pathway in Cardiac Remodeling and Heart Failure
Zhou, S., Sun, W., Zhang, Z., & Zheng, Y. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/260429 · Cited by 205
Oncogenic functions of the transcription factor Nrf2
Gañán‐Gómez, I., Wei, Y., Yang, H., Boyano-Adánez, M. C., & Garcia‐Manero, G. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.06.041 · Cited by 203
Cardozo, L., Pedruzzi, L. M., Stenvinkel, P., Stockler‐Pinto, M. B., Daleprane, J. B., Leite, M., & Mafra, D. (2013) · Biochimie · doi:10.1016/j.biochi.2013.04.012 · Cited by 202
Kanzaki, H., Shinohara, F., Kajiya, M., & Kodama, T. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.478545 · Cited by 201
Recurrent Loss of NFE2L2 Exon 2 Is a Mechanism for Nrf2 Pathway Activation in Human Cancers
Goldstein, L. D., Lee, J., Gnad, F., Klijn, C. N., Schaub, A., Reeder, J., Daemen, A., Bakalarski, C. E., Holcomb, T., Shames, D. S., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.010 · Cited by 205
Jang, J., Wang, Y., Kim, H.-S., Lalli, M. A., & Kosik, K. S. (2014) · Stem Cells · doi:10.1002/stem.1764 · Cited by 203
Nrf2 as a target for cancer chemoprevention
Yu, X. Y., & Kensler, T. W. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.04.017 · Cited by 199
Miller, V. J., Villamena, F. A., & Volek, J. S. (2018) · Journal of Nutrition and Metabolism · doi:10.1155/2018/5157645 · Cited by 205
Targeting the Nrf2–Keap1 antioxidant defence pathway for neurovascular protection in stroke
Alfieri, A., Srivastava, S., Siow, R. C. M., Modo, M., Fraser, P. A., & Mann, G. E. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.210294 · Cited by 198
Theodore, M., Kawai, Y., Yang, J., Kleshchenko, Y. Y., Reddy, S. P., Villalta, F., & Arinze, I. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m709040200 · Cited by 202
The pleiotropic functions of reactive oxygen species in cancer
Wu, K., Zowalaty, A. E. E., Sayin, V. I., & Papagiannakopoulos, T. Y. (2024) · Nature Cancer · doi:10.1038/s43018-024-00738-9 · Cited by 216
Redox control of cell proliferation
Chiu, J., & Dawes, I. W. (2012) · Trends in Cell Biology · doi:10.1016/j.tcb.2012.08.002 · Cited by 201
Wild, A. C., & Mulcahy, R. (2000) · Free Radical Research · doi:10.1080/10715760000300291 · Cited by 197
The KEAP1–NRF2 System as a Molecular Target of Cancer Treatment
Taguchi, K., & Yamamoto, M. (2020) · Cancers · doi:10.3390/cancers13010046 · Cited by 195
“As an approach to delineate the domain function, a yeast two-hybrid screen was conducted using the Neh2 domain as bait, and we identified a new molecule, KEAP1 [20].”
BackgroundMethodInfluentialSelf-citationNitric Oxide in Cell Survival: A Janus Molecule
Calabrese, V., Cornelius, C., Rizzarelli, E., Owen, J. B., Dinkova‐Kostova, A. T., & Butterfield, D. A. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2721 · Cited by 198
Yu, R., Mandlekar, S., Lei, W., Fahl, W. E., Tan, T., & Kong, A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.4.2322 · Cited by 196
Chapple, S., Cheng, X.-H., & Mann, G. (2013) · Redox Biology · doi:10.1016/j.redox.2013.04.001 · Cited by 183
Nuclear Import and Export Signals in Control of Nrf2
Jain, A. K., Bloom, D. A., & Jaiswal, A. K. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502083200 · Cited by 195
RetractedMolecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism
Horie, Y., Suzuki, T., Inoue, J., Iso, T., Wells, G., Moore, T. W., Mizushima, T., Dinkova‐Kostova, A. T., Kasai, T., Kamei, T., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02100-6 · Cited by 195
Self-citationRegulation of Nrf2 Transactivation Domain Activity
Shen, G., Hebbar, V., Nair, S., Xu, C., Li, W., Lin, W., Keum, Y.-S., Han, J., Gallo, M. A., & Kong, A.-N. T. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401368200 · Cited by 194
Zhong, C.-C., Zhao, T., Högstrand, C., Chen, F., Song, C.-C., & Luo, Z. (2021) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2021.108883 · Cited by 197
DJ-1 induces thioredoxin 1 expression through the Nrf2 pathway
Im, J., Lee, K.-W., Woo, J.-M., Junn, E., & Mouradian, M. M. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds131 · Cited by 197
Li, X., Zhang, T., Lv, W., Wang, H., Chen, H., Xu, Q., Cai, H., & Dai, J. (2022) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2022.113238 · Cited by 207
Li, J., Lee, J., & Johnson, J. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109380200 · Cited by 193
Niture, S. K., Jain, A. K., & Jaiswal, A. K. (2009) · Journal of Cell Science · doi:10.1242/jcs.058537 · Cited by 192
RetractedThe role of Nrf2 in increased reactive oxygen species and DNA damage in prostate tumorigenesis
Frohlich, D. A., McCabe, M. T., Arnold, R. S., & Day, M. L. (2008) · Oncogene · doi:10.1038/onc.2008.79 · Cited by 192
Pro-Oxidant Activity of Flavonoids Induces EpRE-Mediated Gene Expression
Lee-Hilz, Y. Y., Boerboom, A.-M. J. F., Westphal, A. H., van Berkel, W. J. H., Aarts, J. M. M. J. G., & Rietjens, I. M. C. M. (2006) · Chemical Research in Toxicology · doi:10.1021/tx060157q · Cited by 192
Sites of alkylation of human Keap1 by natural chemoprevention agents
Luo, Y., Eggler, A. L., Liu, D., Liu, G., Mesecar, A. D., & van Breemen, R. B. (2007) · Journal of the American Society for Mass Spectrometry · doi:10.1016/j.jasms.2007.09.015 · Cited by 191
Methylation of the KEAP1 gene promoter region in human colorectal cancer
Hanada, N., Takahata, T., Zhou, Q., Ye, X., Sun, R., Itoh, J., Ishiguro, A., Kijima, H., Mimura, J., Itoh, K., et al. (2012) · BMC Cancer · doi:10.1186/1471-2407-12-66 · Cited by 189
Self-citationTargeting the KEAP1-NRF2 system to prevent kidney disease progression
Nezu, M., Suzuki, N., & Yamamoto, M. (2017) · American Journal of Nephrology · doi:10.1159/000475890 · Cited by 3,447
Self-citationThe Nrf2 Pathway in Liver Diseases
Zhou, J., Zheng, Q., & Chen, Z. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.826204 · Cited by 204
The Keap1–Nrf2 system as an in vivo sensor for electrophiles
Uruno, A., & Motohashi, H. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.02.007 · Cited by 187
NRF2: KEAPing Tumors Protected
Pillai, R., Hayashi, M., Zavitsanou, A.-M., & Papagiannakopoulos, T. Y. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0922 · Cited by 196
Hu, R., Saw, C. L. L., Yu, R., & Kong, A. T. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3276 · Cited by 190
Shen, G., & Kong, A. T. (2009) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.680 · Cited by 185
Kahn, N., Rea, S. L., Moyle, S. S., Kell, A. M., & Johnson, T. (2008) · Biochemical Journal · doi:10.1042/bj20070521 · Cited by 192
NRF2 Activation in Cancer: From DNA to Protein
Cloer, E. W., Goldfarb, D., Schrank, T. P., Weissman, B. E., & Major, M. B. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2723 · Cited by 182
Neuron-Astrocyte Interactions in Parkinson’s Disease
Miyazaki, I., & Asanuma, M. (2020) · Cells · doi:10.3390/cells9122623 · Cited by 186
Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance
Raghunath, A., Sundarraj, K., Arfuso, F., Sethi, G., & Perumal, E. (2018) · Cancers · doi:10.3390/cancers10120481 · Cited by 187
Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway
Sondermann, N. C., Faßbender, S., Hartung, F., Hätälä, A. M., Rolfes, K. M., Vogel, C. F. A., & Haarmann‐Stemmann, T. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115371 · Cited by 205
Metadata
- Authors
- Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M.
- Affiliations
- University of Tsukuba (JP)
- Northwestern University (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1999-01-01
- Volume
- 13
- Issue
- 1
- Pages
- 76-86
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC316370
- OpenAlex
- W2115338196
- Cited by
- 3,634
- References
- 46
- Citations by year
- 2026: 141 · 2025: 162 · 2024: 177 · 2023: 196 · 2022: 222 · 2021: 184 · 2020: 217 · 2019: 196 · 2018: 187 · 2017: 197 · 2016: 177 · 2015: 177 · 2014: 167 · 2013: 162 · 2012: 142
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (R01CA080088, CA 80088)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- Keap1, Nrf2, antioxidant response element, oxidative stress sensing, phase II enzymes, reactive oxygen species, transcriptional repression, oxidative stress response
- MeSH terms
- Amino Acid Sequence, Animals, Antioxidants, Birds, Carrier Proteins, Cell Line, DNA-Binding Proteins, Fungal Proteins, Gene Expression Regulation, Luminescent Proteins, Molecular Sequence Data, Protein Binding, Recombinant Fusion Proteins, Transcription Factors, Transfection, Transcriptional Activation, Trans-Activators, Conserved Sequence, Sequence Homology, Amino Acid, Genes, Reporter, Oxidative Stress, Saccharomyces cerevisiae Proteins, Green Fluorescent Proteins, NF-E2-Related Factor 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review