Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling
Open accessAbstract
Keap1 is a BTB-Kelch substrate adaptor protein that regulates steady-state levels of Nrf2, a bZIP transcription factor, in response to oxidative stress. We have determined the structure of the Kelch domain of Keap1 bound to a 16-mer peptide from Nrf2 containing a highly conserved DxETGE motif. The Nrf2 peptide contains two short antiparallel beta-strands connected by two overlapping type I beta-turns stabilized by the aspartate and threonine residues. The beta-turn region fits into a binding pocket on the top face of the Kelch domain and the glutamate residues form multiple hydrogen bonds with highly conserved residues in Keap1. Mutagenesis experiments confirmed the role of individual amino acids for binding of Nrf2 to Keap1 and for Keap1-mediated repression of Nrf2-dependent gene expression. Our results provide a detailed picture of how a BTB-Kelch substrate adaptor protein binds to its cognate substrate and will enable the rational design of novel chemopreventive agents.
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
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?
Crystal structures of peptide substrate complexes have been reported for four BTB-Kelch family members, including KEAP1, KLHL2, KLHL3 and KLHL20.
“Crystal structures of peptide substrate complexes have been reported for four BTB-Kelch family members, including KEAP1, KLHL2, KLHL3 and KLHL20 (refs 80,81,82 ).”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [80]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
1 retracted
RETRACTED ARTICLE: Genetic alterations of the NRP/B gene are associated with human brain tumors
Liang, X.-Q., Avraham, H. K., Jiang, S., & Avraham, S. (2004) · Oncogene · doi:10.1038/sj.onc.1207776 · Cited by 47 · see citing works
Retracted<i>Coot</i> : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571 · see citing works
The PyMOL Molecular Graphics System
DeLano, W. L. (2002) · Medical Entomology and Zoology · Cited by 18,147 · see citing works
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,671 · see citing works
Oxidants, oxidative stress and the biology of ageing
Finkel, T., & Holbrook, N. J. (2000) · Nature · doi:10.1038/35041687 · Cited by 9,413 · see citing works
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 · see citing works
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 · see citing works
Imlay, J. A. (2003) · Annual Review of Microbiology · doi:10.1146/annurev.micro.57.030502.090938 · Cited by 2,201 · see citing works
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 · see citing works
Use of TLS parameters to model anisotropic displacements in macromolecular refinement
Winn, M., Isupov, M. N., & Murshudov, G. N. (2001) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444900014736 · Cited by 1,701 · see citing works
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 · see citing works
Zhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480 · see citing works
Self-citationKeap1 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 1,262 · see citing works
Self-citationThe finer things in X-ray diffraction data collection
Pflugrath, J. W. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744499900935x · Cited by 1,244 · see citing works
Main-chain Bond Lengths and Bond Angles in Protein Structures
Laskowski, R. A., Moss, D. S., & Thornton, J. M. (1993) · Journal of Molecular Biology · doi:10.1006/jmbi.1993.1351 · Cited by 1,217 · see citing works
The structure of the G protein heterotrimer Giα1β1γ2
Wall, M. A., Coleman, D. E., Lee, E. N., Iñiguez-Lluhı́, J. A., Posner, B. A., Gilman, A. G., & Sprang, S. R. (1995) · Cell · doi:10.1016/0092-8674(95)90220-1 · Cited by 1,124 · see citing works
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 · see citing works
Cullinan, 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 · see citing works
Efficient anisotropic refinement of macromolecular structures using FFT
Murshudov, G. N., Vagin, A. A., Lebedev, A., Wilson, K. S., & Dodson, E. J. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s090744499801405x · Cited by 937 · see citing works
Kobayashi, A., Kang, M.-I., Watai, Y., Tong, K. I., Shibata, T., Uchida, K., & Yamamoto, M. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.221-229.2006 · Cited by 933 · see citing works
Vaguine, A. A., Richelle, J., & Wodak, S. J. (1999) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444998006684 · Cited by 887 · see citing works
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 · see citing works
Oxidative Stress, Antioxidant Defenses, and Damage Removal, Repair, and Replacement Systems
Davies, K. J. A. (2000) · IUBMB Life · doi:10.1080/713803728 · Cited by 774 · see citing works
Structure of an HIF-1α-pVHL Complex: Hydroxyproline Recognition in Signaling
Min, J.-H., Yang, H., Ivan, M., Gertler, F., Kaelin, W. G., & Pavletich, N. P. (2002) · Science · doi:10.1126/science.1073440 · Cited by 765 · see citing works
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 12× · see citing works
“…Biology Organization The EMBO Journal VOL 25 | NO 15 | 2006 3613 second Keap1 binding site in Nrf2, containing the consensus sequence LxxQDxDLG and located at a distance of approximately 50 amino acids on the N-terminal side of the DxETGE motif, has recently been identified (Tong et al, 2006).”
BackgroundMethodInfluentialStructural basis for the recognition of hydroxyproline in HIF-1α by pVHL
Hon, W.-C., Wilson, M. I., Harlos, K., Claridge, T. D. W., Schofield, C. J., Pugh, C. W., Maxwell, P. H., Ratcliffe, P. J., Stuart, D. I., & Jones, E. Y. (2002) · Nature · doi:10.1038/nature00767 · Cited by 751 · see citing works
Furukawa, M., & Xiong, Y. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.25.1.162-171.2005 · Cited by 746 · see citing works
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 11× · see citing works
“As expected, both of these mutant Keap1 proteins are impaired in their ability to bind Nrf2 (Padmanabhan et al, 2006).”
BackgroundResultInfluentialSequence and structural analysis of BTB domain proteins
Stogios, P. J., Downs, G. S., Jauhal, J. J., Nandra, S. K., & Privé, G. G. (2005) · Genome Biology · doi:10.1186/gb-2005-6-10-r82 · Cited by 694 · see citing works
The contribution of endogenous sources of DNA damage to the multiple mutations in cancer
Jackson, A. L., & Loeb, L. A. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00091-4 · Cited by 630 · see citing works
Structure 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 · see citing works
Oxidative Stress, Antioxidant Defenses, and Damage Removal, Repair, and Replacement Systems
Davies, K. J. A. (2000) · IUBMB Life · doi:10.1080/15216540051081010 · Cited by 608 · see citing works
Katoh, 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 521 · see citing works
Orlicky, S. M., Tang, X., Willems, A. R., Tyers, M., & Sicheri, F. (2003) · Cell · doi:10.1016/s0092-8674(03)00034-5 · Cited by 510 · see citing works
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 459 · see citing works
Motohashi, 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 · see citing works
Glucose and reactive oxygen species
Bonnefont‐Rousselot, D. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200209000-00016 · Cited by 455 · see citing works
Bomont, P., Cavalier, L., Blondeau, F., Hamida, C. B., Belal, S., Tazir, M., Demir, E., Topaloğlu, H., Korinthenberg, R., Tüysüz, B., et al. (2000) · Nature Genetics · doi:10.1038/81701 · Cited by 408 · see citing works
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 406 · see citing works
Hong, F., Freeman, M. L., & Liebler, D. C. (2005) · Chemical Research in Toxicology · doi:10.1021/tx0502138 · Cited by 404 · see citing works
The Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm
Zipper, L. M., & Mulcahy, R. T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206530200 · Cited by 366 · see citing works
Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast.
Chan, J. Y., Han, X. L., & Kan, Y. W. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.11371 · Cited by 342 · see citing works
Identification of the interactive interface and phylogenic conservation of the Nrf2‐Keap1 system
Kobayashi, M., Itoh, K., Suzuki, T., Osanai, H., Nishikawa, K., Katoh, Y., Takagi, Y., & Yamamoto, M. P. (2002) · Genes to Cells · doi:10.1046/j.1365-2443.2002.00561.x · Cited by 340 · see citing works
Wu, G., Xu, G., Schulman, B. A., Jeffrey, P. D., Harper, J. W., & Pavletich, N. P. (2003) · Molecules and Cells · Cited by 333 · see citing works
Specific Patterns of Electrophile Adduction Trigger Keap1 Ubiquitination and Nrf2 Activation
Hong, F., Sekhar, K. R., Freeman, M. L., & Liebler, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503346200 · Cited by 316 · see citing works
Leung, L., Kwong, M., Hou, S., Lee, C., & Chan, J. Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308439200 · Cited by 299 · see citing works
Zhang, D. D., Lo, S., Sun, Z., Habib, G. M., Lieberman, M. W., & Hannink, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501279200 · Cited by 299 · see citing works
Self-citationDhakshinamoorthy, S., & Jaiswal, A. K. (2001) · Oncogene · doi:10.1038/sj.onc.1204506 · Cited by 290 · see citing works
Aruoma, O. I., Halliwell, B. B., & DPhil, B. H. (1993) · Medical Entomology and Zoology · Cited by 283 · see citing works
Crystal Structure of the Kelch Domain of Human Keap1
Li, X., Zhang, D. D., Hannink, M., & Beamer, L. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410073200 · Cited by 249 · see citing works
Self-citationKatoh, 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 212 · see citing works
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 · see citing works
Strategies to reduce oxidative stress in cardiovascular disease
Hamilton, C. A., MILLER, W. H., Al‐Benna, S., Brosnan, M. J., DRUMMOND, R. D., McBride, M., & Dominiczak, A. F. (2004) · Clinical Science · doi:10.1042/cs20030379 · Cited by 189 · see citing works
Oxidative stress in cardiovascular disease: myth or fact?
Ceconi, C., Boraso, A., Cargnoni, A., & Ferrari, R. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.06.002 · Cited by 171 · see citing works
Axis determination by inhibition of Wnt signaling in XenopusPreprint
Itoh, K., & Sokol, S. Y. (1999) · Genes & Development · doi:10.1101/gad.13.17.2328 · Cited by 163 · see citing works
Mhatre, M., Floyd, R. A., & Hensley, K. (2004) · Journal of Alzheimer s Disease · doi:10.3233/jad-2004-6206 · Cited by 147 · see citing works
Antioxidant and cytoprotective responses to redox stress
Mathers, J. E., Fraser, J. A., McMahon, M. J., Saunders, R. D. C., Hayes, J. D., & McLellan, L. I. (2004) · Biochemical Society Symposia · doi:10.1042/bss0710157 · Cited by 134 · see citing works
酵母での遺伝的選択によるNF-E2関連転写因子、Nrf1のクローニング
Chan, J. Y., X‐L, H., & W, K. Y. (1993) · Cited by 123 · see citing works
Factors governing the foldability of proteins
Klimov, D. K., & Thirumalai, D. (1996) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(199612)26:4 · Cited by 115 · see citing works
Bloom, D. A., Dhakshinamoorthy, S., & Jaiswal, A. K. (2002) · Oncogene · doi:10.1038/sj.onc.1205288 · Cited by 101 · see citing works
CAND1-Mediated Substrate Adaptor Recycling Is Required for Efficient Repression of Nrf2 by Keap1
Lo, S., & Hannink, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.4.1235-1244.2006 · Cited by 99 · see citing works
Self-citationWang, W., Ding, J., Allen, K. E., Zhu, P., Zhang, L., Vogel, H. S., & Yang, Y. (2005) · Current Biology · doi:10.1016/j.cub.2005.10.052 · Cited by 96 · see citing works
Nrf2 Possesses a Redox-insensitive Nuclear Export Signal Overlapping with the Leucine Zipper Motif
Li, W., Jain, M. R., Chen, C., Yue, X., Hebbar, V., Zhou, R., & Kong, A.-N. T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m410601200 · Cited by 95 · see citing works
Oxidative damage in cultured human olfactory neurons from Alzheimer's disease patients
Ghanbari, H. A., Ghanbari, K., Harris, P. L. R., Jones, P. K., Kubat, Z., Castellani, R. J., Wolozin, B. L., Smith, M. A., & Perry, G. L. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00083.x · Cited by 85 · see citing works
Clinical and molecular findings in patients with giant axonal neuropathy (GAN)
Bruno, C., Bertini, E., Federico, A., Tonoli, E., Lispi, M. L., Cassandrini, D., Pedemonte, M., Santorelli, F. M., Filocamo, M., Dotti, M. T., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000101676.41505.a7 · Cited by 66 · see citing works
Giant axonal neuropathy (GAN): Case report and two novel mutations in the gigaxonin gene
Kuhlenbäumer, G., Young, P., Oberwittler, C., Hünermund, G., Schirmacher, A., Domschke, K., Ringelstein, B. E., & Stögbauer, F. (2002) · Neurology · doi:10.1212/wnl.58.8.1273 · Cited by 59 · see citing works
Identification of seven novel mutations in theGAN gene
Bomont, P., Ioos, C., Yalçınkaya, C., Korinthenberg, R., Vallat, J., Assami, S., Münnich, A., Chabrol, B., Kurlemann, G., Tazir, M., et al. (2003) · Human Mutation · doi:10.1002/humu.9122 · Cited by 49 · see citing works
Therapeutic Potential in Alzheimer Disease
Cash, A., Perry, G. L., & Smith, M. (2002) · Current Medicinal Chemistry · doi:10.2174/0929867023369411 · Cited by 22 · see citing works
A keaper and a striker maintain epidermal homeostasis
Magin, T. M. (2003) · Nature Genetics · doi:10.1038/ng1103-202 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Hooft RW, Sander C, Vriend G (1996) Positioning hydrogen atoms by optimizing hydrogen-bond networks in protein structures. Proteins 26: 363–376 [DOI] [PubMed] [Google Scholar]
Cited by
Sorted by citations
Role of nrf2 in oxidative stress and toxicity
Ma, Q. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140320 · Cited by 4,903 · see citing works
ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis
D'Autréaux, B., & Toledano, M. B. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2256 · Cited by 3,642 · see citing works
The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway
Baird, L., & Yamamoto, M. P. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00099-20 · Cited by 1,600 · see citing works
Ubiquitin ligases: structure, function, and regulation
Zheng, N., & Shabek, N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014922 · Cited by 1,499 · see citing works
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 · see citing works
The emerging role of the Nrf2–Keap1 signaling pathway in cancerPreprint
Jaramillo, M. C., & Zhang, D. D. (2013) · Genes & Development · doi:10.1101/gad.225680.113 · Cited by 1,304 · see citing works
Small molecules, big targets: drug discovery faces the protein–protein interaction challenge
Scott, D. E., Bayly, A. R., Abell, C., & Skidmore, J. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.29 · Cited by 1,137 · see citing works
Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130 · see citing works
The cytoprotective role of the Keap1–Nrf2 pathway
Baird, L., & Dinkova‐Kostova, A. T. (2011) · Archives of Toxicology · doi:10.1007/s00204-011-0674-5 · Cited by 1,029 · see citing works
Lu, H., Zhou, Q., He, J., Jiang, Z., Peng, C., Tong, R., & Shi, J. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00315-3 · Cited by 891 · see citing works
Targeted protein degradation: expanding the toolbox
Schapira, M., Calabrese, M. F., Bullock, A. N., & Crews, C. M. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0047-y · Cited by 960 · see citing works
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 · see citing works
The eIF2α kinases: their structures and functions
Donnelly, N., Gorman, A. M., Gupta, S., & Afshin Samali, A. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1252-6 · Cited by 860 · see citing works
The Keap1–Nrf2–ARE Pathway As a Potential Preventive and Therapeutic Target: An Update
Lu, M., Ji, J., Jiang, Z., & You, Q. (2016) · Medicinal Research Reviews · doi:10.1002/med.21396 · Cited by 807 · see citing works
Stress-activated cap’n’collar transcription factors in aging and human disease
Sykiotis, G. P., & Bohmann, D. (2010) · Science Signaling · doi:10.1126/scisignal.3112re3 · Cited by 776 · see citing works
Molecular mechanisms of Nrf2‐mediated antioxidant response
Li, W., & Kong, A. T. (2008) · Molecular Carcinogenesis · doi:10.1002/mc.20465 · Cited by 786 · see citing works
Surh, Y., Kundu, J. K., & Na, H. (2008) · Planta Medica · doi:10.1055/s-0028-1088302 · Cited by 759 · see citing works
Magesh, S., Chen, Y., & Hu, L. (2012) · Medicinal Research Reviews · doi:10.1002/med.21257 · Cited by 760 · see citing works
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 · see citing works
Genetic landscape of esophageal squamous cell carcinoma
Gao, Y., Chen, Z.-L., Li, J.-G., Hu, X.-D., Shi, X.-J., Sun, Z.-M., Zhang, F., Zhao, Z.-R., Li, Z.-T., Liu, Z.-Y., et al. (2014) · Nature Genetics · doi:10.1038/ng.3076 · Cited by 697 · see citing works
LAU, A., VILLENEUVE, N., Sun, Z., Wong, P. K., & Zhang, D. (2008) · Pharmacological Research · doi:10.1016/j.phrs.2008.09.003 · Cited by 645 · see citing works
Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities
Boyden, L. M., Choi, M., Choate, K. A., Nelson-Williams, C. J., Farhi, A., Toka, H. R., Tikhonova, I. R., Bjornson, R. D., Mane, S., Colussi, G., et al. (2012) · Nature · doi:10.1038/nature10814 · Cited by 641 · see citing works
Transcription Factor NRF2 as a Therapeutic Target for Chronic Diseases: A Systems Medicine Approach
Cuadrado, A., Manda, G., Hassan, A., Alcaraz, M. J., Barbas, C., Daiber, A., Ghezzi, P., León, R., López, M. G., Oliva, B., et al. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014753 · Cited by 632 · see citing works
Activators and Inhibitors of NRF2: A Review of Their Potential for Clinical Development
Robledinos-Antón, N., Fernández-Ginés, R., Manda, G., & Cuadrado, A. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/9372182 · Cited by 608 · see citing works
Structural basis of Keap1 interactions with Nrf2
Canning, P., Sorrell, F. J., & Bullock, A. N. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.05.034 · Cited by 605 · see citing works
Piantadosi, C. A., Carraway, M. S., Babiker, A., & Suliman, H. B. (2008) · Circulation Research · doi:10.1161/01.res.0000338597.71702.ad · Cited by 580 · see citing works
Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors
Brigelius‐Flohé, R., & Flohé, L. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3534 · Cited by 576 · see citing works
The integrated landscape of driver genomic alterations in glioblastoma
Frattini, V., Trifonov, V., Chan, J. M., Castano, A. M., Lia, M., Abate, F., Keir, S. T., Ji, A. X., Zoppoli, P., Niola, F., et al. (2013) · Nature Genetics · doi:10.1038/ng.2734 · Cited by 543 · see citing works
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 540 · see citing works
The Cullin-RING Ubiquitin-Protein Ligases
Hua, Z., & Vierstra, R. D. (2011) · Annual Review of Plant Biology · doi:10.1146/annurev-arplant-042809-112256 · Cited by 509 · see citing works
Nrf2/Keap1/ARE signaling: Towards specific regulation
Ulasov, A. V., Rosenkranz, A. A., Georgiev, G. P., & Sobolev, A. S. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.120111 · Cited by 520 · see citing works
Zhuang, M., Calabrese, M. F., Liu, J., Waddell, M. B., Nourse, A., Hammel, M., Miller, D. J., Walden, H., Duda, D. M., Seyedin, S. N., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.022 · Cited by 486 · see citing works
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 474 · see citing works
Tong, K. I., Padmanabhan, B., Kobayashi, A., Shang, C., Hirotsu, Y., Yokoyama, S., & Yamamoto, M. P. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00753-07 · Cited by 447 · see citing works
Signal amplification in the KEAP1-NRF2-ARE antioxidant response pathway
Liu, S., Pi, J., & Zhang, Q. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102389 · Cited by 445 · see citing works
Solis, L. M., Behrens, C., Dong, W., Suraokar, M. B., Ozburn, N. C., Moran, C. A., Corvalán, A. H., Biswal, S. S., Swisher, S. G., Bekele, B. N., et al. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-3352 · Cited by 430 · see citing works
Canonical and non-canonical mechanisms of Nrf2 activation
Silva‐Islas, C. A., & Maldonado, P. D. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.06.013 · Cited by 393 · see citing works
A metabolite-derived protein modification integrates glycolysis with KEAP1–NRF2 signalling
Bollong, M. J., Lee, G., Coukos, J. S., Yun, H., Zambaldo, C., Chang, J. W., Chin, E. N., Ahmad, I., Chatterjee, A. K., Lairson, L. L., et al. (2018) · Nature · doi:10.1038/s41586-018-0622-0 · Cited by 344 · see citing works
Keap1, the cysteine-based mammalian intracellular sensor for electrophiles and oxidants
Dinkova‐Kostova, A. T., Kostov, R. V., & Canning, P. (2016) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2016.08.005 · Cited by 332 · see citing works
The Nrf2–Keap1 defence pathway: Role in protection against drug-induced toxicity
Copple, I. M., Goldring, C. E., Kitteringham, N. R., & Park, B. K. (2007) · Toxicology · doi:10.1016/j.tox.2007.10.029 · Cited by 328 · see citing works
Abed, D. A., Goldstein, M., Albanyan, H., Jin, H., & Hu, L. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.05.008 · Cited by 330 · see citing works
Molecular Basis of Electrophilic and Oxidative Defense: Promises and Perils of Nrf2
Ma, Q., & He, X. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.004333 · Cited by 317 · see citing works
PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria
Lo, S.-C., & Hannink, M. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.02.014 · Cited by 300 · see citing works
Self-citationDavies, T. G., Wixted, W. E., Coyle, J. E., Griffiths-Jones, C., Hearn, K., McMenamin, R., Norton, D., Rich, S. J., Richardson, C., Saxty, G., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00228 · Cited by 322 · see citing works
PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage
Bobrovnikova-Marjon, E. V., Grigoriadou, C., Pytel, D., Zhang, F., Ye, J., Koumenis, C., Cavener, D. R., & Diehl, J. A. (2010) · Oncogene · doi:10.1038/onc.2010.153 · Cited by 302 · see citing works
Structural basis for Cul3 protein assembly with the BTB-Kelch family of E3 ubiquitin ligases
Canning, P., Cooper, C. D. O., Krojer, T., Murray, J. W., Pike, A. C. W., Chaikuad, A., Keates, T., Thangaratnarajah, C., Hojzan, V., Marsden, B. D., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.437996 · Cited by 284 · see citing works
“Finally, the Kelch domain and substrate from the KEAP1-Nrf2 complex (PDB 2FLU) (51) were modeled atop helix 14 of the BACK domain of KLHL11.”
InfluentialThe hallmarks of P arkinson's disease
Antony, P. M. A., Diederich, N. J., Krüger, R., & Balling, R. (2013) · FEBS Journal · doi:10.1111/febs.12335 · Cited by 301 · see citing works
Singh, S., Vrishni, S., Singh, B. K., Rahman, I., & Kakkar, P. (2010) · Free Radical Research · doi:10.3109/10715762.2010.507670 · Cited by 294 · see citing works
Genschik, P., Sumara, I., & Lechner, E. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.173 · Cited by 278 · see citing works
Crisman, E., Duarte, P., Daudén, E., Cuadrado, A., Rodrı́guez-Franco, M. I., López, M. G., & Leon, R. M. (2022) · Medicinal Research Reviews · doi:10.1002/med.21925 · Cited by 273 · see citing works
Beyond repression of Nrf2: An update on Keap1
Kopacz, A., Klóska, D., Forman, H. J., Józkowicz, A., & Grochot‐Przeczek, A. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.03.023 · Cited by 262 · see citing works
Jiang, Z., Lu, M., Xu, L., Yang, T., Xi, M., Xu, X., Guo, X., Zhang, X., You, Q., & Sun, H.-P. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5000529 · Cited by 263 · see citing works
Hast, B. E., Goldfarb, D., Mulvaney, K. M., Hast, M. A., Siesser, P. F., Yan, F., Hayes, D. N., & Major, M. B. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4400 · Cited by 259 · see citing works
Giudice, A., Arra, C., & Turco, M. C. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-738-9_3 · Cited by 254 · see citing works
Shibata, S., Zhang, J., Puthumana, J., Stone, K. L., & Lifton, R. P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1304592110 · Cited by 253 · see citing works
Piantadosi, C. A., Withers, C. M., Bartz, R. R., MacGarvey, N. C., Fu, P. P., Sweeney, T. E., Welty‐Wolf, K. E., & Suliman, H. B. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.207738 · Cited by 250 · see citing works
Marcotte, D. J., Zeng, W., Hus, J., McKenzie, A., Hession, C., Jin, P., Bergeron, C., Lugovskoy, A. A., Enyedy, I. J., Cuervo, H., et al. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.04.019 · Cited by 245 · see citing works
Rojo, A. I., de Sagarra, M. R., & Cuadrado, A. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05124.x · Cited by 241 · see citing works
Hammad, M., Raftari, M., Cesário, R., Salma, R., Godoy, P. R. D. V., Emami, S. N., & Haghdoost, S. (2023) · Antioxidants · doi:10.3390/antiox12071371 · Cited by 245 · see citing works
Ogura, T., Tong, K. I., Mio, K., Maruyama, Y., Kurokawa, H., Sato, C., & Yamamoto, M. P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914036107 · Cited by 232 · see citing works
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 · see citing works
Ohta, A., Schumacher, F., Mehellou, Y., Johnson, C., Knebel, A., Macartney, T., Wood, N. T., Alessi, D. R., & Kurz, T. (2013) · Biochemical Journal · doi:10.1042/bj20121903 · Cited by 223 · see citing works
Preparation and identification of antioxidant peptides from cottonseed proteins
Wang, L., Ma, M., Yu, Z., & Du, S. (2021) · Food Chemistry · doi:10.1016/j.foodchem.2021.129399 · Cited by 210 · see citing works
Oxidative Stress in Alzheimer’s Disease: Are We Connecting the Dots?
Rosini, M., Simoni, E., Milelli, A., Minarini, A., & Melchiorre, C. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400970m · Cited by 202 · see citing works
Lo, S.-C., & Hannink, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606539200 · Cited by 199 · see citing works
Self-citationComprehensive analysis of loops at protein-protein interfaces for macrocycle design
Gavenonis, J., Sheneman, B. A., Siegert, T. R., Eshelman, M. R., & Kritzer, J. A. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1580 · Cited by 201 · see citing works
An Overview of the Nrf2/ARE Pathway and Its Role in Neurodegenerative Diseases
Zgórzyńska, E., Dziedzic, B., & Walczewska, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179592 · Cited by 207 · see citing works
PALB2 Interacts with KEAP1 To Promote NRF2 Nuclear Accumulation and Function
Ma, J., Cai, H., Wu, T., Sobhian, B., Huo, Y., Alcivar, A. L., Mehta, M., Cheung, K. L., Ganesan, S., Kong, A. T., et al. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06271-11 · Cited by 193 · see citing works
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 184 · see citing works
Cino, E. A., Choy, W., & Karttunen, M. (2012) · Journal of Chemical Theory and Computation · doi:10.1021/ct300323g · Cited by 184 · see citing works
Binding Mode and Structure–Activity Relationships around Direct Inhibitors of the Nrf2–Keap1 Complex
Jnoff, E., Albrecht, C., Barker, J. J., Barker, O., Beaumont, E., Bromidge, S. M., Brookfield, F. A., Brooks, M., Bubert, C., Ceska, T., et al. (2014) · ChemMedChem · doi:10.1002/cmdc.201300525 · Cited by 180 · see citing works
The Keap1–Nrf2 Cell Defense Pathway – A Promising Therapeutic Target?
Copple, I. M. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-398339-8.00002-1 · Cited by 172 · see citing works
Keap Calm, and Carry on Covalently
Wilson, A. J., Kerns, J. K., Callahan, J. F., & Moody, C. J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400224q · Cited by 171 · see citing works
Targeting the Nrf2 pathway against cardiovascular disease
Li, J., Ichikawa, T., Janicki, J. S., & Cui, T. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903025762 · Cited by 168 · see citing works
Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects
Shahcheraghi, S. H., Salemi, F., Peirovi, N., Ayatollahi, J., Alam, W., Khan, H. Z., & Saso, L. (2021) · Molecules · doi:10.3390/molecules27010167 · Cited by 169 · see citing works
Marrot, L., Jones, C., Perez, P., & Meunier, J. (2008) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2007.00424.x · Cited by 164 · see citing works
The Role of NRF2/KEAP1 Signaling Pathway in Cancer Metabolism
Song, M.-Y., Lee, D.-Y., Chun, K., & Kim, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094376 · Cited by 166 · see citing works
Zhuang, C., Narayanapillai, S. C., Zhang, W., Sham, Y. Y., & Xing, C. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm4017174 · Cited by 156 · see citing works
Keap1/Cullin3 Modulates p62/SQSTM1 Activity via UBA Domain Ubiquitination
Lee, Y., Chou, T., Pittman, S. K., Keith, A. L., Razani, B., & Weihl, C. C. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.030 · Cited by 154 · see citing works
Cysteine-based regulation of the CUL3 adaptor protein Keap1
Sekhar, K. R., Rachakonda, G., & Freeman, M. L. (2009) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2009.06.016 · Cited by 153 · see citing works
Fujii, S., Sawa, T., Ihara, H., Tong, K. I., Ida, T., Okamoto, T., Ahmed, K. A., Ishima, Y., Motohashi, H., Yamamoto, M. P., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.145441 · Cited by 151 · see citing works
Peptide inhibitors of the Keap1–Nrf2 protein–protein interaction
Hancock, R., Bertrand, H. C., Tsujita, T., Naz, S., El-Bakry, A., Laoruchupong, J., Hayes, J. D., & Wells, G. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.10.486 · Cited by 147 · see citing works
Mészáros, B., Kumar, M., Gibson, T. J., Uyar, B., & Dosztányi, Z. (2017) · Science Signaling · doi:10.1126/scisignal.aak9982 · Cited by 139 · see citing works
Protein-structure-guided discovery of functional mutations across 19 cancer types
Niu, B., Scott, A. D., Sengupta, S., Bailey, M. H., Batra, P., Ning, J., Wyczalkowski, M. A., Liang, W.-W., Zhang, Q., McLellan, M. D., et al. (2016) · Nature Genetics · doi:10.1038/ng.3586 · Cited by 137 · see citing works
Mutant p53-Associated Molecular Mechanisms of ROS Regulation in Cancer Cells
Cordani, M., Butera, G., Pacchiana, R., Masetto, F., Mullappilly, N., Riganti, C., & Donadelli, M. (2020) · Biomolecules · doi:10.3390/biom10030361 · Cited by 141 · see citing works
Luo, X., Weng, X., Bao, X., Bai, X., Lv, Y., Zhang, S., Chen, Y., Zhao, C., Zeng, M., Huang, J., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102511 · Cited by 141 · see citing works
Innamorato, N. G., Jaźwa, A., Rojo, A. I., García, C., Fernández‐Ruíz, J., Grochot‐Przeczek, A., Stachurska, A., Józkowicz, A., Dulak, J., & Cuadrado, A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011838 · Cited by 138 · see citing works
Cancer-Derived Mutations in KEAP1 Impair NRF2 Degradation but not Ubiquitination
Hast, B. E., Cloer, E. W., Goldfarb, D., Li, H., Siesser, P. F., Yan, F., Walter, V., Zheng, N., Hayes, D. N., & Major, M. B. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-1655 · Cited by 138 · see citing works
Anuranjani, & Bala, M. (2014) · Redox Biology · doi:10.1016/j.redox.2014.02.008 · Cited by 138 · see citing works
Nrf2 activation through the inhibition of Keap1–Nrf2 protein–protein interaction
Lee, S., & Hu, L. (2020) · Medicinal Chemistry Research · doi:10.1007/s00044-020-02539-y · Cited by 136 · see citing works
Liu, P., Zhang, T., Chen, Q., Li, C., Chu, Y., Guo, Q., Zhang, Y., Zhou, W., Chen, H., Zhou, Z., et al. (2021) · Advanced Materials · doi:10.1002/adma.202100746 · Cited by 137 · see citing works
Self-citationCross-cancer profiling of molecular alterations within the human autophagy interaction network
Lebovitz, C. B., Robertson, A. G., Goya, R., Jones, S. J. M., Morin, R. D., Marra, M. A., & Gorski, S. M. (2015) · Autophagy · doi:10.1080/15548627.2015.1067362 · Cited by 133 · see citing works
Rojo, A. I., Rada, P., Egea, J., Rosa, A. O., López, M. G., & Cuadrado, A. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.06.007 · Cited by 132 · see citing works
Zhang, Y., & Xiang, Y. (2016) · Biochemical Journal · doi:10.1042/bj20151182 · Cited by 125 · see citing works
Camp, N. D., James, R. G., Dawson, D. W., Yan, F., Davison, J. M., Houck, S. A., Tang, X., Zheng, N., Major, M. B., & Moon, R. T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.316471 · Cited by 128 · see citing works
Tonolo, F., Fiorese, F., Moretto, L., Folda, A., Scalcon, V., Grinzato, A., Ferro, S., Arrigoni, G., Bindoli, A., Feller, E., et al. (2020) · Antioxidants · doi:10.3390/antiox9020117 · Cited by 133 · see citing works
KEAP1, a cysteine-based sensor and a drug target for the prevention and treatment of chronic disease
Naidu, S. D., & Dinkova‐Kostova, A. T. (2020) · Open Biology · doi:10.1098/rsob.200105 · Cited by 129 · see citing works
Luo, X., Wang, Y., Zhu, X., Chen, Y., Xu, B., Bai, X., Weng, X., Xu, J., Tao, Y., Yang, D., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102987 · Cited by 128 · see citing works
Farr, S. A., Ripley, J. L., Rukhsana Sultana, A., Zhang, Z., Niehoff, M. L., Platt, T. L., Murphy, M. P., Morley, J. E., Kumar, V. B., & Butterfield, D. A. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.11.014 · Cited by 127 · see citing works
Jiang, Z., Lu, M., & You, Q. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00586 · Cited by 126 · see citing works
- Authors
- Lo, S., Li, X., Henzl, M. T., Beamer, L. J., & Hannink, M.
- Affiliations
- University of Missouri (US)
- Corresponding author
- Beamer, Lesa J
- Hannink, Mark
- Venue
- The EMBO Journal
- Published
- 2006-08-03
- Volume
- 25
- Issue
- 15
- Pages
- 3605-3617
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1538563
- OpenAlex
- W2141982524
- Cited by
- 604
- References
- 68
- Citations by year
- 2026: 66 · 2025: 66 · 2024: 44 · 2023: 48 · 2022: 47 · 2021: 36 · 2020: 35 · 2019: 23 · 2018: 22 · 2017: 21 · 2016: 25 · 2015: 25 · 2014: 22 · 2013: 34 · 2012: 22
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P50CA103130)
- National Center for Complementary and Integrative Health (AT003899, R01AT003899)
- Lawrence Berkeley National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- Keap1, Nrf2, Kelch domain, protein-protein interaction, beta-turn, oxidative stress response, chemoprevention, protein structure
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Amino Acid Sequence, Animals, Binding Sites, Cells, Cultured, Chlorocebus aethiops, Humans, Models, Molecular, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Conformation, Signal Transduction, Conserved Sequence, Protein Structure, Tertiary, Dimerization, COS Cells, Amino Acid Motifs, Intracellular Signaling Peptides and 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