The DOI matches its Crossref record; 109 of the 109 references it cites were found in a registry or an index.
The Keap1-Nrf2 system and diabetes mellitus
Open accessAbstract
Nrf2 (NF-E2-related factor 2) plays a key role in the protection of vertebrates against environmental stress by contributing to the inducible expression of detoxification and antioxidant enzymes. Keap1 (Kelch-like ECH-associated protein 1) is a sensor for oxidative and electrophilic stresses. Keap1 also acts as an E3 ubiquitin ligase substrate-recognition subunit that specifically targets Nrf2. Keap1 causes Nrf2 to be degraded through the ubiquitin-proteasome pathway and thus ensures that Nrf2 is constitutively suppressed under unstressed conditions. Upon exposure to oxidative or electrophilic stress, Keap1 loses its ability to ubiquitinate Nrf2. Many lines of evidence have recently clarified that the Keap1-Nrf2 system also plays critical roles in the maintenance of cellular homeostasis. One of the most salient examples is the contribution of Keap1-Nrf2 to metabolic and energy-balance regulation. In particular, how the Keap1-Nrf2 system protects the body against diabetes mellitus and how perturbations in this system provoke the disease condition are now under intense investigation. This review will summarize the recent progress made in this area.
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“despite its beneficial role in cellular protection and cancer prevention, Nrf2 also has a harmful “dark side” in cancer [156].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [156]
Citations
Cites
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Cited by
Sorted by citations
Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases
Cuadrado, A., Rojo, A. I., Wells, G., Hayes, J. D., Cousin, S. P., Rumsey, W. L., Attucks, O. C., Franklin, S., Levonen, A., Kensler, T. W., et al. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0008-x · Cited by 1,510
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
Molecular basis of the Keap1–Nrf2 system
Suzuki, T., & Yamamoto, M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.006 · Cited by 995
Self-citationTu, W., Wang, H., Li, S., Liu, Q., & Sha, H. (2018) · Aging and Disease · doi:10.14336/ad.2018.0513 · Cited by 727
“Numerous evidences have recently elucidated the role of Keap1–Nrf2 system in metabolic and energy-balance regulation [103].”
BackgroundInfluentialSKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans
Blackwell, T. K., Steinbaugh, M. J., Hourihan, J. M., Ewald, C. Y., & Isik, M. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.008 · Cited by 622
“various aspects of metabolism and other functions [1,3–5].”
Metadata
- Authors
- Uruno, A., Yagishita, Y., & Yamamoto, M.
- Affiliations
- Tohoku University (JP)
- Corresponding author
- Uruno, Akira
- Yamamoto, Masayuki
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 566
- Pages
- 76-84
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W2091259533
- Cited by
- 231
- References
- 109
- Citations by year
- 2026: 15 · 2025: 7 · 2024: 19 · 2023: 20 · 2022: 26 · 2021: 23 · 2020: 28 · 2019: 24 · 2018: 20 · 2017: 13 · 2016: 16 · 2015: 20
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Archives of Biochemistry and Biophysics (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Science, Sports and Culture
- Create Revolutionary Technological Seeds for Science and Technology Innovation program (CREST) of the Japanese Technology Agency
- Japan Society for the Promotion of Science (24249015, 90396474, 26893008)
- Takeda Foundation
- Naito Foundation
- Japanese Foundation for Applied Enzymology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- Keap1, Nrf2, diabetes mellitus, oxidative stress, electrophilic stress, ubiquitin-proteasome system, E3 ubiquitin ligase, antioxidant defense, metabolic homeostasis, energy balance
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Animals, Diabetes Mellitus, Type 2, Gene Expression Regulation, Humans, Signal Transduction, Oxidative Stress, Ubiquitin-Protein Ligases, Proteasome Endopeptidase Complex, Intracellular Signaling Peptides and Proteins, Insulin-Secreting Cells, NF-E2-Related Factor 2, Ubiquitination, Proteolysis
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