The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis.
By Masayuki Yamamoto, T. Kensler, Hozumi Motohashi. Physiological Reviews, 2018
1,708 citations recorded by the source corpus.
The Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) system forms the major node of cellular and organismal defense against oxidative and electrophilic stresses of both exogenous and endogenous origins. KEAP1 acts as a cysteine thiol-rich sensor of redox insults, whereas NRF2 is a transcription factor that robustly transduces chemical signals to regulate a battery of cytoprotective genes. KEAP1 represses NRF2 activity under quiescent conditions, whereas NRF2 is liberated from KEAP1-mediated repression on exposure to stresses. The rapid inducibility of a response based on a derepression mechanism is an important feature of the KEAP1-NRF2 system. Recent studies have unveiled the complexities of the functional contributions of the KEAP1-NRF2 system and defined its broader involvement in biological processes, including cell proliferation and differentiation, as well as cytoprotection. In this review, we describe historical milestones in the initial characterization of the KEAP1-NRF2 system and provide a comprehensive overview of the molecular mechanisms governing the functions of KEAP1 and NRF2, as well as their roles in physiology and pathology. We also refer to the clinical significance of the KEAP1-NRF2 system as an important prophylactic and therapeutic target for various diseases, particularly aging-related disorders. We believe that controlled harnessing of the KEAP1-NRF2 system is a key to healthy aging and well-being in humans.
Subfields: Molecular Biology, Rheumatology
View Paper: https://www.semanticscholar.org/paper/2709b8f82ddc3d4151815a458a9d678878b0c2b9
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In Molecular Biology
- A. Dinkova-Kostova
- Liam Baird
- Masayuki Yamamoto
- J. Hayes
- K. Tew
- Donna D. Zhang
- Hozumi Motohashi
- A. Abramov
Citations in the corpus
- Oxidative Stress in Cancer (2020, background): “As shown in Table 1, NRF2 transactivates a wide spectrum of antioxidant genes upon exposure to ROS or soft electrophiles (Hayes Dinkova-Kostova, 2014; Hayes JD; Yamamoto et al., 2018).”
- The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway (2020, background): “Through the regulation of cytoprotective gene expression, the KEAP1-NRF2 stress response pathway is the principal inducible defense against oxidative and electrophilic stresses (5).”