The DOI matches its Crossref record; 84 of the 84 references it cites were found in a registry or an index.
Molecular basis of the Keap1–Nrf2 system
Open accessAbstract
Nrf2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. Nrf2 induces the expression of detoxification and antioxidant enzymes, and Keap1 (Kelch-like ECH-associated protein 1), an adaptor subunit of Cullin 3-based E3 ubiquitin ligase, regulates Nrf2 activity. Keap1 also acts as a sensor for oxidative and electrophilic stresses. Keap1 retains multiple sensor cysteine residues that detect various stress stimuli. Increasing attention has been paid to the roles that Nrf2 plays in the protection of our bodies against drug toxicity and stress-induced diseases. On the other hand, Nrf2 is found to promote both oncogenesis and cancer cell resistance against chemotherapeutic drugs. Thus, although Nrf2 acts to protect our body from deleterious stresses, cancer cells hijack the Nrf2 activity to support their malignant growth. Nrf2 has emerged as a new therapeutic target, and both inducers and inhibitors of Nrf2 are awaited. Studies challenging the molecular basis of the Keap1-Nrf2 system functions are now critically important to improve translational studies of the system. Indeed, recent studies identified cross talk between Nrf2 and other signaling pathways, which provides new insights into the mechanisms by which the Keap1-Nrf2 system serves as a potent regulator of our health and disease.
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“The transcription factor Nrf2 is considered as a redox switch regulating the expression of antioxidant enzymes, GSH-synthesizing enzymes, and detoxifying Phase 2 enzymes (175), while the specific selenocysteine tRNA is needed for the synthesis of selenoproteins such as GPx or Trx reductase, which reduces oxidized Trx (133) (Fig. 2).”
From Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia (2017) · cites this paper as [175]
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Self-citationKomatsu, 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
Self-citationOncogene-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
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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
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-citationNrf2–Keap1 defines a physiologically important stress response mechanism
Motohashi, H., & Yamamoto, M. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.003 · Cited by 1,725
Self-citationZhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480
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
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Nrf2-Keap1 signaling in oxidative and reductive stress
Bellezza, I., Giambanco, I., Minelli, A., & Donato, R. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2018.02.010 · Cited by 2,134
Kurutas, E. B. (2015) · Nutrition Journal · doi:10.1186/s12937-016-0186-5 · Cited by 2,152
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
Cragg, G. M. L., & Pezzuto, J. M. (2015) · Medical Principles and Practice · doi:10.1159/000443404 · Cited by 845
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 815
Metadata
- Authors
- Suzuki, T., & Yamamoto, M.
- Affiliations
- Tohoku University (JP)
- Corresponding author
- Yamamoto, Masayuki
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 88
- Issue
- Pt B
- Pages
- 93-100
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W952491933
- Cited by
- 995
- References
- 84
- Citations by year
- 2026: 62 · 2025: 89 · 2024: 83 · 2023: 102 · 2022: 116 · 2021: 104 · 2020: 118 · 2019: 88 · 2018: 78 · 2017: 82 · 2016: 62 · 2015: 10
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 360 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Free Radical Biology and Medicine (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Japan Science and Technology Agency
- Japan Society for the Promotion of Science (26460354, 2611010, 24249015, 25112502)
- Takeda Science Foundation
- Naito Foundation
- Core Research for Evolutional Science and Technology
- 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, oxidative stress sensing, electrophilic stress, chemoresistance, carcinogenesis, Nrf2 inhibitors, Nrf2 inducers, therapeutic target
- MeSH terms
- Animals, Humans, Signal Transduction, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2
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