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Beyond repression of Nrf2: An update on Keap1
Free Radical Biology and Medicine, 2020 Nrf2 (NFE2L2 - nuclear factor (erythroid-derived 2)-like 2) is a transcription factor, which is repressed by interaction with a redox-sensitive protein Keap1 (Kelch-like ECH-associated protein 1). Deregulation of Nrf2 transcriptional activity has been described in the pathogenesis of multiple diseases, and the Nrf2/Keap1 axis has emerged as a crucial ...
Henry Jay Forman +2 more
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Nature Cancer, 2020
KEAP1 is a tumor suppressor encoded by a gene commonly mutated in lung cancer. A systematic search for Keap1-mutant cancer vulnerabilities now reveals that Slc33a1 is a context-specific essential gene that represents a promising new anti-cancer target.
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KEAP1 is a tumor suppressor encoded by a gene commonly mutated in lung cancer. A systematic search for Keap1-mutant cancer vulnerabilities now reveals that Slc33a1 is a context-specific essential gene that represents a promising new anti-cancer target.
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Role of human Keap1 S53 and S293 residues in modulating the binding of Keap1 to Nrf2
Biochimie, 2019Keap1 is deemed as a suppressor of Nrf2 in cytoplasm by sequestrating Nrf2 to proteolysis as an adapter of the Cul3-Rbx1 E3 ubiquitin ligase complex. In the study, it was proposed that post-translational modification might affect the interaction between Nrf2 and Keap1, and the profiles of the phosphorylation of amino acid residues of Keap1 and its ...
Shuangshuang Wei +7 more
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Cell Chemical Biology
In this issue of Cell Chemical Biology, Lu et al.1 report the discovery of a bivalent KEAP1 inhibitor (biKEAP1), which more rapidly activates NRF2 compared to previously reported monovalent KEAP1 inhibitors. biKEAP1suppresses acute inflammation in animal models.
Jan, Gerhartz, Radosław P, Nowak
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In this issue of Cell Chemical Biology, Lu et al.1 report the discovery of a bivalent KEAP1 inhibitor (biKEAP1), which more rapidly activates NRF2 compared to previously reported monovalent KEAP1 inhibitors. biKEAP1suppresses acute inflammation in animal models.
Jan, Gerhartz, Radosław P, Nowak
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The cytoprotective role of the Keap1–Nrf2 pathway
Archives of Toxicology, 2011An elaborate network of highly inducible proteins protects aerobic cells against the cumulative damaging effects of reactive oxygen intermediates and toxic electrophiles, which are the major causes of neoplastic and chronic degenerative diseases. These cytoprotective proteins share common transcriptional regulation, through the Keap1-Nrf2 pathway ...
Baird, Liam, Dinkova-Kostova, Albena T.
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Role of the Keap1–Nrf2 Pathway in Cancer
2014The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) pathway is one of the major signaling cascades involved in cell defense and survival against endogenous and exogenous stress. While Nrf2 and its target genes provide protection against various age-related diseases including tumorigenesis, constitutively active ...
Levonen Anna-Liisa +4 more
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The Keap1–Nrf2 system and diabetes mellitus [PDF]
Archives of Biochemistry and Biophysics, 2015 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.
Masayuki Yamamoto +2 more
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Development of Novel Inhibitors for Keap1-Nrf2 and Keap1-P62 Protein-Protein Interaction
Free Radical Biology and Medicine, 2016Nrf2-Keap1 system is a biological defense mechanism in response to various stressors. An inhibitor for Keap1-Nrf2 interaction to activate Nrf2 is expected as a novel target for drug discovery in oxidative stress-related disorders. However, Nrf2 is accumulated in many types of cancer and its expression is induced during the course of drug resistance ...
Daisuke Yasuda +14 more
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Mechanism of the Nrf2/Keap1/ARE signaling system
Biochemistry (Moscow), 2011Nrf2 regulates expression of genes containing antioxidant-respons(iv)e element (ARE) in their promoters and plays a pivotal role among all redox-sensitive transcription factors. Nrf2 is constitutively controlled by repressor protein Keap1, which acts as a molecular sensor of disturbances in cellular homeostasis.
V O, Tkachev +2 more
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Keap1 as the redox sensor of the antioxidant response
Archives of Biochemistry and Biophysics, 2017Reactive oxygen species (ROS) and products of their reactions with cellular macromolecules such as unsaturated fatty acids have been implicated to be important regulators of signalling processes via oxidation or alkylation of redox active thiol residues in target proteins. One of key redox-sensitive signalling proteins mediating the response to oxidant
Virve, Sihvola, Anna-Liisa, Levonen
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