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Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease
Open accessAbstract
Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulates the basal and stress-inducible expression of a battery of genes encoding key components of the glutathione-based and thioredoxin-based antioxidant systems, as well as aldo-keto reductase, glutathione S-transferase, and Nad(p)h quinone oxidoreductase-1 drug-metabolizing isoenzymes along with multidrug-resistance-associated efflux pumps. It therefore plays a pivotal role in both intrinsic resistance and cellular adaptation to reactive oxygen species (ROS) and xenobiotics. Activation of Nrf2 can, however, serve as a double-edged sword because some of the genes it induces may contribute to chemical carcinogenesis by promoting futile redox cycling of polycyclic aromatic hydrocarbon metabolites or confer resistance to chemotherapeutic drugs by increasing the expression of efflux pumps, suggesting its cytoprotective effects will vary in a context-specific fashion. In addition to cytoprotection, Nrf2 also controls genes involved in intermediary metabolism, positively regulating those involved in NADPH generation, purine biosynthesis, and the β-oxidation of fatty acids, while suppressing those involved in lipogenesis and gluconeogenesis. Nrf2 is subject to regulation at multiple levels. Its ability to orchestrate adaptation to oxidants and electrophiles is due principally to stress-stimulated modification of thiols within one of its repressors, the Kelch-like ECH-associated protein 1 (Keap1), which is present in the cullin-3 RING ubiquitin ligase (CRL) complex CRLKeap1. Thus modification of Cys residues in Keap1 blocks CRLKeap1 activity, allowing newly translated Nrf2 to accumulate rapidly and induce its target genes. The ability of Keap1 to repress Nrf2 can be attenuated by p62/sequestosome-1 in a mechanistic target of rapamycin complex 1 (mTORC1)-dependent manner, thereby allowing refeeding after fasting to increase Nrf2-target gene expression. In parallel with repression by Keap1, Nrf2 is also repressed by β-transducin repeat-containing protein (β-TrCP), present in the Skp1-cullin-1-F-box protein (SCF) ubiquitin ligase complex SCFβ-TrCP. The ability of SCFβ-TrCP to suppress Nrf2 activity is itself enhanced by prior phosphorylation of the transcription factor by glycogen synthase kinase-3 (GSK-3) through formation of a DSGIS-containing phosphodegron. However, formation of the phosphodegron in Nrf2 by GSK-3 is inhibited by stimuli that activate protein kinase B (PKB)/Akt. In particular, PKB/Akt activity can be increased by phosphoinositide 3-kinase and mTORC2, thereby providing an explanation of why antioxidant-responsive element-driven genes are induced by growth factors and nutrients. Thus Nrf2 activity is tightly controlled via CRLKeap1 and SCFβ-TrCP by oxidative stress and energy-based signals, allowing it to mediate adaptive responses that restore redox homeostasis and modulate intermediary metabolism. Based on the fact that Nrf2 influences multiple biochemical pathways in both positive and negative ways, it is likely its dose-response curve, in terms of susceptibility to certain degenerative disease, is U-shaped. Specifically, too little Nrf2 activity will lead to loss of cytoprotection, diminished antioxidant capacity, and lowered β-oxidation of fatty acids, while conversely also exhibiting heightened sensitivity to ROS-based signaling that involves receptor tyrosine kinases and apoptosis signal-regulating kinase-1. By contrast, too much Nrf2 activity disturbs the homeostatic balance in favor of reduction, and so may have deleterious consequences including overproduction of reduced glutathione and NADPH, the blunting of ROS-based signal transduction, epithelial cell hyperplasia, and failure of certain cell types to differentiate correctly. We discuss the basis of a putative U-shaped Nrf2 dose-response curve in terms of potentially competing processes relevant to different stages of tumorigenesis.
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“This interaction is mediated by a 349DPSTGE354 motif in p62’s Keap1-interacting region (KIR) that resembles the ETGE motif in the Keap1-binding domain of Nrf2 [79,80,81].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [79]
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“In response to elevated levels of reactive oxygen species (ROS) and environmental toxins or to nutrient and metabolic changes through mTOR signaling and insulin/IGF signaling, NRF/SKN-1 activates the expression of genes involved in cellular protection (Blackwell et al., 2015; Tebay et al., 2015).”
From The Aging Epigenome (2016) · cites this paper as Tebay et al., 2015
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Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351
Toxic potential of materials at the nanolevel
Nel, A., Xia, T., Mädler, L., & Li, N. (2006) · Science · doi:10.1126/science.1114397 · Cited by 9,324
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989
Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex
Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M. (2005) · Science · doi:10.1126/science.1106148 · Cited by 6,216
The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Walter, P., & Ron, D. (2011) · Science · doi:10.1126/science.1209038 · Cited by 5,897
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732
Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+
Bootman, M. D., Missiaen, L., Parys, J. B., SMEDT, H. D., & Casteels, R. (1995) · Biochemical Journal · doi:10.1042/bj3060445 · Cited by 5,131
Comprehensive genomic characterization of head and neck squamous cell carcinomas
The Cancer Genome Atlas Network (2015) · Nature · doi:10.1038/nature14129 · Cited by 4,147
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
Comprehensive genomic characterization of squamous cell lung cancers
The Cancer Genome Atlas Research Network (2012) · Nature · doi:10.1038/nature11404 · Cited by 3,994
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630
Hayes, J. D., Flanagan, J. U., & Jowsey, I. R. (2004) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.45.120403.095857 · Cited by 3,565
Self-citationHereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Valente, E. M., Abou-Sleiman, P. M., Caputo, V., Muqit, M. M. K., Harvey, K., Gispert, S., Ali, Z., Del Turco, D., Bentivoglio, A. R., Healy, D. G., et al. (2004) · Science · doi:10.1126/science.1096284 · Cited by 3,481
Hayes, J. D., & Pulford, D. J. (1995) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409239509083491 · Cited by 3,464
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
The Consensus Coding Sequences of Human Breast and Colorectal Cancers
Sjöblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D. L., Leary, R. J., Ptak, J., Silliman, N., et al. (2006) · Science · doi:10.1126/science.1133427 · Cited by 3,161
THE MAMMALIAN UNFOLDED PROTEIN RESPONSE
Schröder, M., & Kaufman, R. J. (2005) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.074134 · Cited by 3,099
Discovery and saturation analysis of cancer genes across 21 tumour types
Lawrence, M. S., Stojanov, P., Mermel, C. H., Robinson, J. T., Garraway, L. A., Golub, T. R., Meyerson, M., Gabriel, S. B., Lander, E. S., & Getz, G. (2014) · Nature · doi:10.1038/nature12912 · Cited by 3,096
TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling
Inoki, K., Li, Y., Zhu, T., Wu, J., & Guan, K.-L. (2002) · Nature Cell Biology · doi:10.1038/ncb839 · Cited by 3,083
Wendel, A. (1981) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(81)77046-0 · Cited by 3,032
The chemical diversity and distribution of glucosinolates and isothiocyanates among plants
Fahey, J. W., Zalcmann, A. T., & Talalay, P. (2001) · Phytochemistry · doi:10.1016/s0031-9422(00)00316-2 · Cited by 2,968
Reactive oxygen species in cell signaling
Thannickal, V. J., & Fanburg, B. L. (2000) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2000.279.6.l1005 · Cited by 2,950
Comprehensive molecular characterization of urothelial bladder carcinoma
Perou, C. M. (2014) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/za09-dk57 · Cited by 2,922
Comprehensive molecular characterization of urothelial bladder carcinoma
Weinstein, J. N., Akbani, R., Broom, B. M., Wang, W., Verhaak, R. G. W., Liu, W., Ju, Z., Motter, T., Peng, B., Ryan, M., et al. (2014) · Nature · doi:10.1038/nature12965 · Cited by 2,746
mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
O'Reilly, K. E., Rojo, F., She, Q.-B., Solit, D., Mills, G. B., Smith, D., Lane, H., Hofmann, F., Hicklin, D. J., Ludwig, D. L., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-2925 · Cited by 2,561
Mammalian thioredoxin is a direct inhibitor of apoptosis signal‐regulating kinase (ASK) 1
Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K., & Ichijo, H. (1998) · The EMBO Journal · doi:10.1093/emboj/17.9.2596 · Cited by 2,377
Integrating cell-signalling pathways with NF-κB and IKK function
Perkins, N. D. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2083 · Cited by 2,350
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322
The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease
Pickrell, A. M., & Youle, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2014.12.007 · Cited by 2,310
Komatsu, M., Kurokawa, H., Waguri, S., Taguchi, K., Kobayashi, A., Ichimura, Y., Sou, Y.-S., Ueno, I., Sakamoto, A., Tong, K. I., et al. (2010) · Nature Cell Biology · doi:10.1038/ncb2021 · Cited by 2,288
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277
Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224
The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
Hayes, J. D., & Dinkova‐Kostova, A. T. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.002 · Cited by 2,210
Self-citationFunction and regulation of cullin–RING ubiquitin ligases
Petroski, M. D., & Deshaies, R. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1547 · Cited by 2,148
The thioredoxin antioxidant system
Lu, J., & Holmgren, A. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.036 · Cited by 2,055
Glutathione metabolism and its selective modification.
Meister, A. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77815-6 · Cited by 2,012
From endoplasmic-reticulum stress to the inflammatory response
Zhang, K., & Kaufman, R. J. (2008) · Nature · doi:10.1038/nature07203 · Cited by 2,010
Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947
Self-citationBrigelius-Flohé, R., & Maiorino, M. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.11.020 · Cited by 1,904
Kamata, H., Honda, S.-I., Maeda, S., Chang, L., Hirata, H., & Karin, M. (2005) · Cell · doi:10.1016/j.cell.2004.12.041 · Cited by 1,792
Role of Quinones in Toxicology
Bolton, J. L., Trush, M. A., Penning, T. M., Dryhurst, G., & Monks, T. J. (2000) · Chemical Research in Toxicology · doi:10.1021/tx9902082 · Cited by 1,703
Self-citationMoi, 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
Biochemistry of oxidative stress
Halliwell, B. B. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351147 · Cited by 1,591
Inoguchi, T., Li, P., Umeda, F., Yu, H. Y., Kakimoto, M., Imamura, M., Aoki, T., Etoh, T., Hashimoto, T., Naruse, M., et al. (2000) · Diabetes · doi:10.2337/diabetes.49.11.1939 · Cited by 1,577
Hoadley, K. A., Yau, C. S. F., Wolf, D. M., Cherniack, A. D., Tamborero, D., Ng, S., Leiserson, M. D. M., Niu, B., McLellan, M. D., Uzunangelov, V., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.049 · Cited by 1,537
DNA binding sites: representation and discovery
Stormo, G. D. (2000) · Bioinformatics · doi:10.1093/bioinformatics/16.1.16 · Cited by 1,519
Cohen, P., & Frame, S. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096075 · Cited by 1,493
Zhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480
Ishii, T., Itoh, K., Takahashi, S., Sato, H., Yanagawa, T., Katoh, Y., Bannai, S., & Yamamoto, M. P. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.21.16023 · Cited by 1,473
Jain, A., Lamark, T., Sjøttem, E., Bowitz Larsen, K., Atesoh Awuh, J., Øvervatn, A., McMahon, M., Hayes, J. D., & Johansen, T. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.118976 · Cited by 1,472
Self-citationOxidative stress, insulin signaling, and diabetes
Rains, J., & Jain, S. K. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.12.006 · Cited by 1,468
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
GSK3 takes centre stage more than 20 years after its discovery
FRAME, S., & COHEN, P. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3590001 · Cited by 1,433
Leslie, E. M., Deeley, R. G., & Cole, S. P. C. (2004) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2004.10.012 · Cited by 1,407
Nrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
Mitsuishi, Y., Taguchi, K., Kawatani, Y., Shibata, T., Nukiwa, T., Aburatani, H., Yamamoto, M., & Motohashi, H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.016 · Cited by 1,395 · cited 10×
“To a greater or lesser extent, these changes will contribute to drug tolerance, inhibition of inflammatory reactions, increase in cell proliferation, and changes in cell differentiation that are observed when Nrf2 is overexpressed [121, 140, 159, 185].”
InfluentialKeap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex
Zhang, D. D., Lo, S., Cross, J. V., Templeton, D. J., & Hannink, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10941-10953.2004 · Cited by 1,284
Wattenberg, L. W. (2008) · Springer eBooks · doi:10.1007/978-1-4020-6754-9_2795 · Cited by 1,244
Phosphorylation of p62 Activates the Keap1-Nrf2 Pathway during Selective Autophagy
Ichimura, Y., Waguri, S., Sou, Y., Kageyama, S., Hasegawa, J., Ishimura, R., Saito, T., Yang, Y., Kouno, T., Fukutomi, T., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.08.003 · Cited by 1,243
(2002) · PubMed · Cited by 1,190
Linker, R. A., Lee, D.-H., Ryan, S., van Dam, A. M., Conrad, R., Bista, P., Zeng, W., Hronowsky, X., Buko, A., Chollate, S., et al. (2011) · Brain · doi:10.1093/brain/awq386 · Cited by 1,155
McMahon, M., Itoh, K., Yamamoto, M., & Hayes, J. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300931200 · Cited by 1,141
Self-citationThe SCF ubiquitin ligase: insights into a molecular machine
Cardozo, T., & Pagano, M. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1471 · Cited by 1,114
Ramos-Gomez, M., Kwak, M.-K., Dolan, P. M., Itoh, K., Yamamoto, M., Talalay, P., & Kensler, T. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051618798 · Cited by 1,102
Huang, H.-C., Nguyen, T., & Pickett, C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206911200 · Cited by 1,070
Dysfunctional KEAP1–NRF2 Interaction in Non-Small-Cell Lung Cancer
Singh, A., Misra, V., Thimmulappa, R. K., Lee, H., Ames, S., Hoque, M. O., Herman, J. G., Baylin, S. B., Sidransky, D., Gabrielson, E., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030420 · Cited by 1,060
Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
Thimmulappa, R. K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25790 · Cited by 1,028 · cited 1×
“Inflammatory responses are exacerbated in the absence of Nrf2—In addition to being susceptible to acute chemical toxicity, Nrf2−/− mice are more susceptible to the proinflammatory effects of allergens, lipopolysaccharide, and a high-fat diet [162, 183, 184].”
Peroxisome Proliferator-Activated Receptor Alpha Target Genes
Rakhshandehroo, M., Knoch, B., Müller, M., & Kersten, S. (2010) · PPAR Research · doi:10.1155/2010/612089 · Cited by 1,020
Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
Hamanaka, R. B., & Chandel, N. S. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.002 · Cited by 1,011
Harris, I. S., Treloar, A. E., Inoue, S., Sasaki, M., Gorrini, C., Lee, K. C., Yung, K. Y., Brenner, D., Knobbe-Thomsen, C. B., Cox, M. A., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.11.019 · Cited by 993
Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke–induced emphysema in mice
Rangasamy, T., Cho, C. Y., Thimmulappa, R. K., Zhen, L., Srisuma, S., Kensler, T. W., Yamamoto, M. P., Petrache, I., Tuder, R. M., & Biswal, S. S. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21146 · Cited by 993
Wakabayashi, N., Dinkova-Kostova, A. T., Holtzclaw, W. D., Kang, M.-I., Kobayashi, A., Yamamoto, M., Kensler, T. W., & Talalay, P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307301101 · Cited by 986 · cited 1×
“Mouse embryonic fibroblast (MEF) cells and macrophages from Nrf2−/− mice possess only about 25% of the intracellular levels of GSH of wild-type MEF cells [140, 141], and this is associated with reduced expression of antioxidant genes such as Gclc, Gclm, Prdx1 (also called MSP23), Slc7a11, Txn1, and Txnrd1[140, 142, 14…”
Self-citationCullinan, S. B., Gordan, J. D., Jin, J., Harper, J. W., & Diehl, J. A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.19.8477-8486.2004 · Cited by 986
Parkinson's disease: from monogenic forms to genetic susceptibility factors
Lesage, S., & Brice, A. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp012 · Cited by 976
Mitochondrial dysfunction and oxidative stress in Parkinson's disease
Subramaniam, S., & Chesselet, M. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.04.004 · Cited by 953
Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate
Salmeen, A., Andersen, J. N., Myers, M. P., Meng, T.-C., Hinks, J. A., Tonks, N. K., & Barford, D. (2003) · Nature · doi:10.1038/nature01680 · Cited by 951
Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation
Wakabayashi, N., Itoh, K., Wakabayashi, J., Motohashi, H., Noda, S., Takahashi, S., Imakado, S., KOTSUJI, T., Otsuka, F., Roop, D. R., et al. (2003) · Nature Genetics · doi:10.1038/ng1248 · Cited by 881
NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer
Hayes, J. D., & McMahon, M. J. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.12.008 · Cited by 870
Self-citationGlutathione-Associated Enzymes In Anticancer Drug Resistance
Tew, K. D. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-3143 · Cited by 853
Lau, A., Wang, X.-J., Zhao, F. L., Villeneuve, N. F., Wu, T., Jiang, T., Sun, Z., White, E., & Zhang, D. D. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00248-10 · Cited by 852
Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2
Wang, X.-J., Sun, Z., Villeneuve, N. F., Zhang, S., Zhao, F., Li, Y., Chen, W., Yi, X., Zheng, W., Wondrak, G. T., et al. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn095 · Cited by 839
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., O'Connor, T., & Yamamoto, M. P. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00640.x · Cited by 828
Clements, C. M., McNally, R. S., Conti, B. J., Mak, T. W., & Ting, J. P.-Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607260103 · Cited by 818
Malhotra, D., Portales-Casamar, É., Singh, A., Srivastava, S., Arenillas, D. J., Happel, C., Shyr, C., Wakabayashi, N., Kensler, T. W., Wasserman, W. W., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq212 · Cited by 812
CYP2E1 and oxidative liver injury by alcohol
Lu, Y., & Cederbaum, A. I. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.11.004 · Cited by 805
Lee, J., Calkins, M. J., Chan, K., Kan, Y. W., & Johnson, J. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211558200 · Cited by 783
Cullinan, S. B., & Diehl, J. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314219200 · Cited by 766
Deeley, R. G., Westlake, C., & Cole, S. P. C. (2006) · Physiological Reviews · doi:10.1152/physrev.00035.2005 · Cited by 761
Gupta, S. C., Hevia, D., Patchva, S., Park, B., Koh, W., & Aggarwal, B. B. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4414 · Cited by 759
Rada, P., Rojo, A. I., Chowdhry, S., McMahon, M., Hayes, J. D., & Cuadrado, A. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.01204-10 · Cited by 759
Self-citationFurukawa, M., & Xiong, Y. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.25.1.162-171.2005 · Cited by 759
Tong, K. I., Katoh, Y., Kusunoki, H., Itoh, K., Tanaka, T., & Yamamoto, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.8.2887-2900.2006 · Cited by 759 · cited 3×
“Hochmuth CE, Biteau B, Bohmann D, Jasper H. Redox regulation by Keap1 and Nrf2 controls intestinal stem cell proliferation in Drosophila.”
Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer
Padmanabhan, B., Tong, K. I., Ohta, T., Nakamura, Y., Scharlock, M., Ohtsuji, M., Kang, M.-I., Kobayashi, A., Yokoyama, S., & Yamamoto, M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.013 · Cited by 735 · cited 1×
“It was first reported that cell lines and tumors from patients with non-small-cell lung carcinoma contain somatic mutations that inactivate Keap1, thereby causing constitutive Nrf2 activation [249, 401].”
Shibata, T., Ohta, T., Tong, K. I., Kokubu, A., Odogawa, R., Tsuta, K., Asamura, H., Yamamoto, M., & Hirohashi, S. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806268105 · Cited by 728
Frame, S., Cohen, P., & Biondi, R. M. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00253-2 · Cited by 724
Mitochondrial Defects and Oxidative Stress in Alzheimer Disease and Parkinson Disease
Yan, M. H., Wang, X., & Zhu, X. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.014 · Cited by 718
Functional antioxidant responsive elements
Wasserman, W. W., & Fahl, W. E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.10.5361 · Cited by 705
Protein kinase C signaling and oxidative stress
Gopalakrishna, R., & Jaken, S. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00221-5 · Cited by 701 · cited 1×
“Activation of PKC isoenzymes by ROS may entail phosphorylation of certain tyrosine residues that lie adjacent to the regulatory domain by non-receptor-type kinases [214], possibly by c-Abl [190], but it may also occur via oxidation of Cys residues in its regulatory or catalytic domains [215].”
Shivdasani, R. A., Rosenblatt, M., Zucker‐Franklin, D., Jackson, C. W., Hunt, P., Saris, C. J. M., & Orkin, S. H. (1995) · Cell · doi:10.1016/0092-8674(95)90531-6 · Cited by 700
Oslowski, C. M., Hara, T., O’Sullivan-Murphy, B., Kanekura, K., Lu, S., Hara, M., Ishigaki, S., Zhu, L. J., Hayashi, E., Hui, S. T. Y., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.07.005 · Cited by 699
Hanschmann, E.-M., Godoy, J. R., Berndt, C., Hudemann, C., & Lillig, C. H. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4599 · Cited by 696
PPARs at the crossroads of lipid signaling and inflammation
Wahli, W., & Michalik, L. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.05.001 · Cited by 692
Antioxidants reduce endoplasmic reticulum stress and improve protein secretion
Malhotra, J. D., Miao, H. Z., Zhang, K., Wolfson, A., Pennathur, S., Pipe, S. W., & Kaufman, R. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809677105 · Cited by 682
Toward clinical application of the Keap1-Nrf2 pathway
Suzuki, T., Motohashi, H., & Yamamoto, M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.04.005 · Cited by 680
Crystal Structure of Glycogen Synthase Kinase 3β
Dajani, R., Fraser, E., Roe, S. M., Young, N., Good, V. M., Dale, T. C., & Pearl, L. H. (2001) · Cell · doi:10.1016/s0092-8674(01)00374-9 · Cited by 680
Kwak, M.-K., Wakabayashi, N., Itoh, K., Motohashi, H., Yamamoto, M. P., & Kensler, T. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211898200 · Cited by 661
McMahon, M. J., Itoh, K., Yamamoto, M. P., Chanas, S. A., Henderson, C. J., McLellan, L. I., Wolf, C. R., Cavin, C., & Hayes, J. D. (2001) · PubMed · Cited by 657
Self-citationChowdhry, S., Zhang, Y., McMahon, M., Sutherland, C., Cuadrado, A., & Hayes, J. D. (2013) · Oncogene · doi:10.1038/onc.2012.388 · Cited by 657
Self-citationOyake, T., Itoh, K., Motohashi, H., Hayashi, N., Hoshino, H., Nishizawa, M., Yamamoto, M. P., & Igarashi, K. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.11.6083 · Cited by 656
PENNING, T. M., BURCZYNSKI, M. E., JEZ, J. M., HUNG, C.-F., LIN, H.-K., MA, H., MOORE, M., PALACKAL, N., & RATNAM, K. (2000) · Biochemical Journal · doi:10.1042/bj3510067 · Cited by 649
Self-citationTOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO
Robida-Stubbs, S., Glover-Cutter, K., Lamming, D. W., Mizunuma, M., Narasimhan, S. D., Neumann-Haefelin, E., Sabatini, D. M., & Blackwell, T. K. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.007 · Cited by 648
Chan, K., Lu, R., Chang, J. C., & Kan, Y. W. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13943 · Cited by 643
Kobayashi, M., Li, L., Iwamoto, N., Nakajima‐Takagi, Y., Kaneko, H., Nakayama, Y., Eguchi, M., Wada, Y., Kumagai, Y., & Yamamoto, M. P. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01080-08 · Cited by 641
Redox regulation of PI 3‐kinase signalling via inactivation of PTEN
Leslie, N. R., Bennett, D., Lindsay, Y. E., Stewart, H., Gray, A., & Downes, C. P. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg513 · Cited by 631
Kwon, J., Lee, S.-R., Yang, K.-S., Ahn, Y., Kim, Y. J., Stadtman, E. R., & Rhee, S. G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407396101 · Cited by 631
Loss of Keap1 Function Activates Nrf2 and Provides Advantages for Lung Cancer Cell Growth
Ohta, T., Iijima, K., Miyamoto, M., Nakahara, I., Tanaka, H., Ohtsuji, M., Suzuki, T., Kobayashi, A., Yokota, J., Sakiyama, T., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-5003 · Cited by 630
Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection
Zhang, M., An, C., Gao, Y., Leak, R. K., Chen, J., & Zhang, F. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.09.003 · Cited by 622
Nrf2 regulates ROS production by mitochondria and NADPH oxidase
Kovac, S., Angelova, P. R., Holmström, K. M., Zhang, Y., Dinkova‐Kostova, A. T., & Abramov, A. Y. (2014) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2014.11.021 · Cited by 621
Self-citationStructure of a β-TrCP1-Skp1-β-Catenin Complex
Wu, G., Xu, G., Schulman, B. A., Jeffrey, P. D., Harper, J. W., & Pavletich, N. P. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00234-x · Cited by 612
Activation of protein kinase C by tyrosine phosphorylation in response to H 2 O 2
Konishi, H., Tanaka, M., Takemura, Y., Matsuzaki, H., Ono, Y., Kikkawa, U., & Nishizuka, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11233 · Cited by 604
AMPK—Sensing Energy while Talking to Other Signaling Pathways
Hardie, D. G. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.09.013 · Cited by 597
Kwak, M.-K., Itoh, K., Yamamoto, M. P., & Kensler, T. W. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.9.2883-2892.2002 · Cited by 597
Adam, J., Hatipoglu, E., O'Flaherty, L., Ternette, N., Sahgal, N., Lockstone, H., Baban, D., Nye, E., Stamp, G. W., Wolhuter, K., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.09.006 · Cited by 585
Reactive oxygen species enhance insulin sensitivity
Loh, K., Deng, H., Fukushima, A., Cai, X., Boivin, B., Galic, S., Bruce, C., Shields, B. J., Skiba, B., Ooms, L. M., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.009 · Cited by 581
Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice
Rangasamy, T., Guo, J., Mitzner, W. A., Roman, J., Singh, A., Fryer, A. D., Yamamoto, M., Kensler, T. W., Tuder, R. M., Georas, S. N., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050538 · Cited by 580
Chen, P.-C., Vargas, M. R., Pani, A. K., Smeyne, R. J., Johnson, D. A., Kan, Y. W., & Johnson, J. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813361106 · Cited by 579
Identification of novel NRF2-regulated genes by ChIP-Seq: influence on retinoid X receptor alpha
Chorley, B. N., Campbell, M. R., Wang, X., Karaca, M., Sambandan, D., Bangura, F., Xue, P., Pi, J., Kleeberger, S. R., & Bell, D. A. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks409 · Cited by 573
Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1
Gonzalez, F. J. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2004.04.021 · Cited by 555
Nrf2 signaling: An adaptive response pathway for protection against environmental toxic insults
Osburn, W. O., & Kensler, T. W. (2007) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2007.11.006 · Cited by 549
Cancer Chemoprevention Mechanisms Mediated Through the Keap1–Nrf2 Pathway
Hayes, J. D., McMahon, M. J., Chowdhry, S., & Dinkova‐Kostova, A. T. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3221 · Cited by 549
Self-citationDJ-1, a novel regulator of the tumor suppressor PTEN
Kim, R. H., Peters, M., Jang, Y., Shi, W., Pintilie, M., Fletcher, G. C., DeLuca, C., Silvester, J., Zhou, L., Snow, B. E., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.02.010 · Cited by 547
Kang, M.-I., Kobayashi, A., Wakabayashi, N., Kim, S.-G., & Yamamoto, M. P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308347100 · Cited by 545
Sasaki, H., Sato, H., Kuriyama-Matsumura, K., Sato, K., Maebara, K., Wang, H., Tamba, M., Itoh, K., Yamamoto, M. P., & Bannai, S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208704200 · Cited by 544
Harvey, C. J., Thimmulappa, R. K., Singh, A., Blake, D. J., Ling, G., Wakabayashi, N., Fujii, J., Myers, A. C., & Biswal, S. S. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.10.040 · Cited by 544
Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species
Bashan, N., Kovsan, J., Kachko, I., Ovadia, H., & Rudich, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00014.2008 · Cited by 542 · cited 1×
“It should, however, be mentioned at the outset that ROS have both positive and negative effects on insulin signaling [225].”
Introduction to Drug Metabolism
Gibson, G. G., & Skett, P. (1994) · Springer eBooks · doi:10.1007/978-1-4899-6844-9 · Cited by 541
Miao, W., Hu, L., Scrivens, P. J., & Batist, G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412081200 · Cited by 541
Direct and indirect antioxidant properties of inducers of cytoprotective proteins
Dinkova‐Kostova, A. T., & Talalay, P. (2008) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.200700195 · Cited by 539
Self-citationKatoh, Y., Itoh, K., Yoshida, E., Miyagishi, M., Fukamizu, A., & Yamamoto, M. P. (2001) · Genes to Cells · doi:10.1046/j.1365-2443.2001.00469.x · Cited by 533
Fujiki, H. (1986) · PubMed · Cited by 528
Salazar‐Roa, M., Rojo, A. I., Velasco, D., de Sagarra, R. M., & Cuadrado, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513737200 · Cited by 523
Bloom, D. A., & Jaiswal, A. K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307633200 · Cited by 523
Rushmore, T. H., & Pickett, C. B. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77351-1 · Cited by 522
Studies on antioxidants: Their carcinogenic and modifying effects on chemical carcinogenesis
Ito, N., Hirose, M., Fukushima, S., Tsuda, H., Shirai, T., & Tatematsu, M. (1986) · Food and Chemical Toxicology · doi:10.1016/0278-6915(86)90291-7 · Cited by 517
Nioi, P., McMahon, M. J., Itoh, K., Yamamoto, M. P., & Hayes, J. D. (2003) · Biochemical Journal · doi:10.1042/bj20030754 · Cited by 515
Self-citationPhysiological Significance of Reactive Cysteine Residues of Keap1 in Determining Nrf2 Activity
Yamamoto, T., Suzuki, T., Kobayashi, A., Wakabayashi, J., Maher, J. M., Motohashi, H., & Yamamoto, M. P. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01704-07 · Cited by 515
Therapeutic Potential of Nrf2 Activators in Streptozotocin-Induced Diabetic Nephropathy
Zheng, H., Whitman, S. A., Wu, W., Wondrak, G. T., Wong, P. K., Fang, D., & Zhang, D. D. (2011) · Diabetes · doi:10.2337/db11-0807 · Cited by 507
GSK-3: Functional Insights from Cell Biology and Animal Models
Kaidanovich‐Beilin, O., & Woodgett, J. R. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00040 · Cited by 505
Antioxidants Enhance Mammalian Proteasome Expression through the Keap1-Nrf2 Signaling Pathway
Kwak, M.-K., Wakabayashi, N., Greenlaw, J. L., Yamamoto, M. P., & Kensler, T. W. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.23.8786-8794.2003 · Cited by 498
Transcriptional regulation of the rat NAD(P)H:quinone reductase gene
Favreau, L. V., & Pickett, C. B. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)64358-7 · Cited by 497
Seki, E., Brenner, D. A., & Karin, M. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.06.004 · Cited by 497
McMahon, M. J., Thomas, N., Itoh, K., Yamamoto, M. P., & Hayes, J. D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601119200 · Cited by 495
Self-citationBae, S. H., Sung, S. H., Oh, S. Y., Lim, J. M., Lee, S. K., Park, Y. N., Lee, H. E., Kang, D., & Rhee, S. G. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.002 · Cited by 492
PKC and the control of localized signal dynamics
Rossé, C., Linch, M. D., Kermorgant, S., Cameron, A. J. M., Boeckeler, K., & Parker, P. J. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2847 · Cited by 488
Orchestrating Redox Signaling Networks through Regulatory Cysteine Switches
Paulsen, C. E., & Carroll, K. S. (2009) · ACS Chemical Biology · doi:10.1021/cb900258z · Cited by 487
Nrf2: friend or foe for chemoprevention?
Kensler, T. W., & Wakabayashi, N. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp231 · Cited by 487
Rada, P., Rojo, A. I., Evrard‐Todeschi, N., Innamorato, N. G., Cotte, A., Jaworski, T., Tobón-Velasco, J. C., Devijver, H., García‐Mayoral, M. F., LEUVEN, F. V., et al. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.00180-12 · Cited by 485
Self-citationJain, A. K., & Jaiswal, A. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611336200 · Cited by 484
Keap1 degradation by autophagy for the maintenance of redox homeostasis
Taguchi, K., Fujikawa, N., Komatsu, M., Ishii, T., Unno, M., Akaike, T., Motohashi, H., & Yamamoto, M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121572109 · Cited by 482
Eggler, A. L., Liu, G., Pezzuto, J. M., van Breemen, R. B., & Mesecar, A. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502402102 · Cited by 476
Shibata, T., Kokubu, A., Gotoh, M., Ojima, H., Ohta, T., Yamamoto, M. P., & Hirohashi, S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.06.082 · Cited by 476
Friling, R. S., Bensimon, A., Tichauer, Y., & Daniel, V. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.16.6258 · Cited by 475
Bonnesen, C., Eggleston, I. M., & Hayes, J. D. (2001) · PubMed · Cited by 463
Self-citationCHANAS, S. A., JIANG, Q., McMAHON, M., McWALTER, G. K., McLELLAN, L. I., ELCOMBE, C. R., HENDERSON, C. J., WOLF, C. R., MOFFAT, G. J., ITOH, K., et al. (2002) · Biochemical Journal · doi:10.1042/bj20020320 · Cited by 460
Self-citationHolmström, K. M., Baird, L., Zhang, Y., Hargreaves, I. P., Chalasani, A., Land, J. M., Stanyer, L., Yamamoto, M. P., Dinkova‐Kostova, A. T., & Abramov, A. Y. (2013) · Biology Open · doi:10.1242/bio.20134853 · Cited by 459
Self-citationMotohashi, H., O'Connor, T., Katsuoka, F., Engel, J. D., & Yamamoto, M. P. (2002) · Gene · doi:10.1016/s0378-1119(02)00788-6 · Cited by 456
Benna, J. E., Dang, P. M., Gougerot‐Pocidalo, M., Marie, J., & Braut‐Boucher, F. (2009) · Experimental & Molecular Medicine · doi:10.3858/emm.2009.41.4.058 · Cited by 453
mTORC1-Activated S6K1 Phosphorylates Rictor on Threonine 1135 and Regulates mTORC2 Signaling
Julien, L.-A., Carriere, A., Moreau, J., & Roux, P. P. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00601-09 · Cited by 452
Denison, M. S., Fisher, J. M., & Whitlock, J. P. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)77819-3 · Cited by 451
McMahon, M. J., Lamont, D. J., Beattie, K. A., & Hayes, J. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007387107 · Cited by 445
Self-citationmTOR and cancer: many loops in one pathway
Efeyan, A., & Sabatini, D. M. (2009) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2009.10.007 · Cited by 441
Penning, T., Burczynski, M., Hung, C. F., McCoull, K. D., Palackal, N., & Tsuruda, L. (1999) · Chemical Research in Toxicology · doi:10.1021/tx980143n · Cited by 440
Self-citationThe Protective Role of Nrf2 in Streptozotocin-Induced Diabetic Nephropathy
Jiang, T., Huang, Z., Lin, Y., Zhang, Z., Fang, D., & Zhang, D. D. (2010) · Diabetes · doi:10.2337/db09-1342 · Cited by 440
Itoh, K., Igarashi, K., Hayashi, N., Nishizawa, M., & Yamamoto, M. P. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.8.4184 · Cited by 438
Rajasekaran, N. S., Connell, P., Christians, E. S., Yan, L.-J., Taylor, R. P., Orosz, A., Zhang, X. Q., Stevenson, T. J., Peshock, R. M., Leopold, J. A., et al. (2007) · Cell · doi:10.1016/j.cell.2007.06.044 · Cited by 437
Quantifying the global cellular thiol–disulfide status
Hansen, R. E., Roth, D., & Winther, J. R. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812149106 · Cited by 437
Nrf2–MafG heterodimers contribute globally to antioxidant and metabolic networks
Hirotsu, Y., Katsuoka, F., Funayama, R., Nagashima, T., Nishida, Y., Nakayama, K., Engel, J. D., & Yamamoto, M. P. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks827 · Cited by 431
McMahon, M. J., Thomas, N., Itoh, K., Yamamoto, M. P., & Hayes, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403061200 · Cited by 419
Self-citationNrf2 Enhances Cell Proliferation and Resistance to Anticancer Drugs in Human Lung Cancer
Homma, S., Ishii, Y., Morishima, Y., Yamadori, T., Matsuno, Y., Haraguchi, N., Kikuchi, N., Satoh, H., Sakamoto, T., Hizawa, N., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-2822 · Cited by 417
Chemical and molecular regulation of enzymes that detoxify carcinogens.
Prestera, T., Holtzclaw, W. D., Zhang, Y., & Talalay, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.7.2965 · Cited by 416
The Keap1–Nrf2 system in cancers: stress response and anabolic metabolism
Mitsuishi, Y., Motohashi, H., & Yamamoto, M. P. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00200 · Cited by 411
Braun, S., Hanselmann, C., Gassmann, M. G., auf dem Keller, U., Born-Berclaz, C., Chan, K., Kan, Y. W., & Werner, S. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5492-5505.2002 · Cited by 410
Role of Nrf2 in the Regulation of CD36 and Stress Protein Expression in Murine Macrophages
Ishii, T., Itoh, K., Ruiz, E., Leake, D. S., Unoki‐Kubota, H., Yamamoto, M. P., & Mann, G. E. (2004) · Circulation Research · doi:10.1161/01.res.0000119171.44657.45 · Cited by 409
Itoh, K., Mochizuki, M., Ishii, Y., Ishii, T., Shibata, T., Kawamoto, Y., Kelly, V., Sekizawa, K., Uchida, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.1.36-45.2004 · Cited by 407 · cited 1×
“During carrageenaninduced acute inflammation, it has been proposed that accumulation of 15-deoxy-Δ12,14prostaglandin J2 in peritoneal macrophages is responsible for activation of Nrf2 through inhibition of Keap1 [194].”
Ooi, A., Wong, J.-C., Petillo, D., Roossien, D., Perrier-Trudova, V., Whitten, D., Min, B. W. H., Tan, M.-H., Zhang, Z., Yang, X. J., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.08.024 · Cited by 401
KEAP1 E3 Ligase-Mediated Downregulation of NF-κB Signaling by Targeting IKKβ
Lee, D.-F., Kuo, H.-P., Liu, M., Chou, C.-K., Xia, W., Du, Y., Shen, J., Chen, C.-T., Huo, L., Hsu, M.-C., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.07.025 · Cited by 399
Satoh, T., Kosaka, K., Itoh, K., Kobayashi, A., Yamamoto, M. P., Shimojo, Y., Kitajima, C., Cui, J., Kamins, J., Okamoto, S., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05039.x · Cited by 399
Baird, L., Llères, D., Swift, S., & Dinkova‐Kostova, A. T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305687110 · Cited by 398
Self-citationStructure of GSK3beta reveals a primed phosphorylation mechanism.
ter Haar, E., Coll, J. T., Austen, D. A., Hsiao, H.-M., Swenson, L. L., & Jain, J. (2001) · Nature Structural Biology · doi:10.1038/89624 · Cited by 394
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Okawa, H., Motohashi, H., Kobayashi, A., Aburatani, H., Kensler, T. W., & Yamamoto, M. P. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.10.185 · Cited by 387
Funato, Y., Michiue, T., Asashima, M., & Miki, H. (2006) · Nature Cell Biology · doi:10.1038/ncb1405 · Cited by 386
Fraenkel, M., Ketzinel‐Gilad, M., Ariav, Y., Pappo, O., Karaca, M., Castel, J., Berthault, M., Magnan, C., Cerasi, E., Kaiser, N., et al. (2008) · Diabetes · doi:10.2337/db07-0922 · Cited by 386
Williams, G. M., Iatropoulos, M. J., & Whysner, J. A. (1999) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(99)00085-x · Cited by 385
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Nioi, P., Nguyen, T., Sherratt, P. J., & Pickett, C. B. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.24.10895-10906.2005 · Cited by 383
Wang, H., Liu, K., Geng, M., Gao, P., Wu, X., Hai, Y., Li, Y., Li, Y., Luo, L., Hayes, J. D., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3386 · Cited by 382
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Metadata
- Authors
- Tebay, L. E., Robertson, H., Durant, S. T., Vitale, S. R., Penning, T. M., Dinkova-Kostova, A. T., & Hayes, J. D.
- Affiliations
- University of Dundee (GB)
- AstraZeneca (United Kingdom) (GB)
- University of Pennsylvania (US)
- Corresponding author
- Hayes, John D.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 88
- Issue
- Pt B
- Pages
- 108-146
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC4659505
- OpenAlex
- W1421415727
- Cited by
- 837
- References
- 514
- Citations by year
- 2026: 56 · 2025: 54 · 2024: 65 · 2023: 89 · 2022: 90 · 2021: 92 · 2020: 103 · 2019: 88 · 2018: 72 · 2017: 75 · 2016: 45 · 2015: 7
- FWCI
- 6.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- Cancer Research UK (C4909/A13786)
- MRC (MR/J001465/1)
- MRC ITTP (1313992)
- BBSRC Industrial CASE (BB/L01405X/1)
- BBSRC (BB/L01923X/1, P30-ES013508)
- 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
- Nrf2, redox stress, Keap1, mTORC1, p62/sequestosome 1, nutrient sensing, energy status, reactive oxygen species, xenobiotic metabolism, drug resistance, multidrug resistance, glutathione, thioredoxin, antioxidant defense, degenerative diseases
- MeSH terms
- Animals, Humans, Oxidation-Reduction, Signal Transduction, Oxidative Stress, NF-E2-Related Factor 2, Carcinogenesis
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