The Antioxidant Defense System Keap1-Nrf2 Comprises a Multiple Sensing Mechanism for Responding to a Wide Range of Chemical Compounds

By Makoto Kobayashi, Li Li, N. Iwamoto, Yaeko Nakajima-Takagi, H. Kaneko, Y. Nakayama, Masami Eguchi, Y. Wada, Y. Kumagai, Masayuki Yamamoto. Molecular and Cellular Biology, 2008

640 citations recorded by the source corpus.

Subfields: Molecular Biology, Safety Research

View Paper: https://www.semanticscholar.org/paper/1efe9cff02eacd1f46e3c48b944d717579867c80

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Citations in the corpus

Role of nrf2 in oxidative stress and toxicity. (2013, background): “In a zebrafish model, Keap1 was shown to recognize a number of electrophilic inducers through distinct sets of cysteine residues, coined “cysteine codes,” to activate Nrf2 (58).”
Antioxidant Properties of Probiotic Bacteria (2017, background): “Nrf2 activation upregulates a series of genes including those involved in xenobiotic and ROS detoxification in order to resist oxidant and electrophilic environmental stressors [73,74].”
Combination therapy in combating cancer (2017, background): “Specifically, the cysteine residues (Cys273 and Cys288) in the intervening linker region of Keap1 are most reactive and sensitive to oxidative changes [36].”
The cytoprotective role of the Keap1–Nrf2 pathway (2011, background): “This suggested that Keap1 contains multiple sensors (Kobayashi et al. 2009).”
The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway (2020, background): “Class I inducers, including the medically relevant bardoxolone, specifically target the Cys151 sensor (120, 125).”
Hydrogen peroxide sensing, signaling and regulation of transcription factors (2014, background): “Human KEAP1 contains 27 cysteine residues, and different agents modify different cysteine residues that translate into specific biological effects [92].”
The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. (2013, background): “prostaglandin J2 [67,74]; PGA2, prostaglandin A2; DEM, diethylmaleate [67] (adapted mRNA and protein levels of a number of Nrf2-regulated genes [58].”
The Roles of NRF2 in Modulating Cellular Iron Homeostasis (2017, background): “KEAP1 regulation of NRF2 is mediated by a series of reactive thiols (23); different cysteines appear to react with different inducers to activate NRF2 (56, 66, 172).”
Mechanisms of activation of the transcription factor Nrf2 by redox stressors, nutrient cues, and energy status and the pathways through which it attenuates degenerative disease (2015, positive): “Cysteine residues that are functionally important or unusual are highlighted: Cys-151 is crucial for the ability of tBHQ and SFN to inhibit the substrate adaptor activity of Keap1 [250], and it forms a transient disulfide bridge with Cys-151 in the other Keap1 subunit [251]; Cys-273 and Cys-288 reco”
Nrf2 is controlled by two distinct β-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. (2012, background): “However, upon treatment of cells with inducing agents (such as sulforaphane or tert- butylhydroquinone) the activity of Keap1 is inhibited, CRLKeap1 no longer ubiquitylates Nrf2, the CNC-bZIP protein accumulates in the nucleus, and ARE-driven genes become transcriptionally activated (12,13).”