ArticleMolecular and cellular biology2016
Characterizations of Three Major Cysteine Sensors of Keap1 in Stress Response.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 2 of them syntheses that pooled it.
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Who cites it
158 citing papers in PubMed, 2 syntheses or guidelines pooled it, 277 citations in OpenAlex.
- A dual-index framework for cold atmospheric plasma dosing: A meta-analysis of parametric control from volumetric redox flux to redox homeostatic status.Redox biology · 2026Pooled it
- The dynamic equilibrium between the protective and toxic effects of matrine in the development of liver injury: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Cysteine-based molecular switches: a focus on KEAP1 and BACH1 in regulating the antioxidant response.Archives of toxicology · 2026Review
- Reactive Oxygen Species in Breast Cancer: From Redox Dysregulation to ROS-Responsive Therapeutics.Cell biochemistry and function · 2026Review
- Compensation for impaired sensing of selenoprotein deficiency by alternative cysteine residues in KEAP1.Redox biology · 2026Article
- Article
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- TrxR Inhibition and Nrf2-FOXO3 Modulation by Repurposed Drugs: A Redox Strategy to Reverse Cancer Multidrug Resistance.Drug development research · 2026Review
- Dietary Polyphenols as Modulators of Redox Signalling: From the Antioxidant-Pro-Oxidant Continuum to Clinical Translation (2015-2025).Current issues in molecular biology · 2026Review
- Nrf2-mediated metabolic reprogramming drives regulatory T cell accumulation in hepatocellular carcinoma.Nature communications · 2026Article
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Diet-Microbiota-Immune Interactions in Hepatocellular Carcinoma: An Immunometabolic and Spatial Perspective.Nutrients · 2026Review
- Article
- Covalent Modification of Keap1 by the Key Metabolic Cofactor Coenzyme A Under Oxidative and Metabolic Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Hexaraphane as a potential therapeutic strategy for tauopathies.Redox biology · 2026Article
- Sex-based differences in the NRF2 oxidative stress response: Implications for precision therapeutics.Redox biology · 2026Review
- NRF2-Targeted Therapy in Cardiovascular Disease Transitions from Systemic Activation to Precision Redox Medicine.Antioxidants (Basel, Switzerland) · 2026Review
- Pathophysiology of reactive oxygen species (ROS).Archives of toxicology · 2026Review
- Altered transposon element-derived genes distort oxygen-free radical scavenger systems in FXD.NAR molecular medicine · 2026Article
- Targeting NRF2 addiction in cancer: synthetic lethal strategies beyond direct inhibition.Frontiers in cell and developmental biology · 2026Review
98 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Keap1-Nrf2 system plays a central role in cytoprotection against electrophilic/oxidative stresses. Although Cys151, Cys273, and Cys288 of Keap1 are major sensor cysteine residues for detecting these stresses, it has not been technically feasible to evaluate the functionality of Cys273 or Cys288, since Keap1 mutants that harbor substitutions in these residues and maintain the ability to repress Nrf2 accumulation do not exist. To overcome this problem, we systematically introduced amino acid substitutions into Cys273/Cys288 and finally identified Cys273Trp and Cys288Glu mutations that do not affect Keap1's ability to repress Nrf2 accumulation. Utilizing these Keap1 mutants, we generated stable murine embryonic fibroblast (MEF) cell lines and knock-in mouse lines. Our analyses with the MEFs and peritoneal macrophages from the knock-in mice revealed that three major cysteine residues, Cys151, Cys273, and Cys288, individually and/or redundantly act as sensors. Based on the functional necessity of these three cysteine residues, we categorized chemical inducers of Nrf2 into four classes. Class I and II utilizes Cys151 and Cys288, respectively, while class III requires all three residues (Cys151/Cys273/Cys288), while class IV inducers function independently of all three of these cysteine residues. This study thus demonstrates that Keap1 utilizes multiple cysteine residues specifically and/or collaboratively as sensors for the detection of a wide range of environmental stresses.
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