Cellular mechanisms of redox cell signalling: role of cysteine modification in controlling antioxidant defences in response to electrophilic lipid oxidation products.

By A. Levonen, A. Landar, A. Ramachandran, E. Ceaser, D. Dickinson, G. Zanoni, J. Morrow, V. Darley-Usmar. Biochemical Journal, 2004

596 citations recorded by the source corpus.

Subfields: Molecular Biology, Organic Chemistry

View Paper: https://www.semanticscholar.org/paper/c134d7df0535b9771f7a80f10af158f42be68247

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Citations in the corpus

Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders (2010, unknown): “We and others have reported that C151, C273, and C288 are of particular importance in the function of Keap1 as a sensor for inducers and as a repressor of Nrf2 (154, 253, 461, 477).”
NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis (2019, background): “shown to adduct to KEAP1 cysteines and activate NRF2 target gene expression [42].”
Oxidative and Electrophilic Stresses Activate Nrf2 through Inhibition of Ubiquitination Activity of Keap1 (2006, background): “Extensive mutation studies in which the cysteine residues were mutated to alanine in a cell culture system demonstrated that Cys273 and Cys288 in the intervening region (IVR) of Keap1 are crucial for its repression activity (25, 39, 43).”
ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis (2007, background): “KeaP1 Cys273 and Cys288, which are among the few reactive Cys residues that have been identified in this protein, are indeed crucial for both zinc coordination and nRF2 degradation 96,98,99 .”
The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway (2020, background): “Subsequent work using cysteine point mutations found that Cys257 and Cys297 were not required for KEAP1’s sensor function and also identified Cys151, which forms an additional stress sensor (109, 110).”
Signaling Functions of Reactive Oxygen Species (2010, background): “Some of the products of lipid peroxidation, initiated by different free radicals, including HO, such as the isoprostanes can signal through receptors (4), while others, such as 4-hydroxy2-nonenal, can participate in signaling by modifying signaling proteins, such as Keap1 (21) or SHP-1, a protein ty”
The Antioxidant Defense System Keap1-Nrf2 Comprises a Multiple Sensing Mechanism for Responding to a Wide Range of Chemical Compounds (2008, background): “This result is consistent with previous reports demonstrating that a Cys-273 mutation reduces the Nrf2-repression activity of mouse Keap1 in cultured cells (25, 43, 46) and in transgenic rescued mice (45).”
Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and disease. (2008, background): “Nrf2 binds to and activates the ,antioxidant response element (ARE),’ also referred to as the ,electrophile response element (EpRE)’ [107].”
The cytoprotective role of the Keap1–Nrf2 pathway (2011, background): “Mutation analysis of the IVR domain showed that substitution of C273 or C288 with either serine or alanine rendered Keap1 unable to repress Nrf2 activity under basal conditions (Zhang and Hannink 2003; Levonen et al. 2004; Wakabayashi et al. 2004).”
Comprehending crystalline β-carotene accumulation by comparing engineered cell models and the natural carotenoid-rich system of citrus (2011, unknown): “Thiol modification by electrophilic lipids has been shown to activate transcription factors, hence inducing gene responses (Levonen et al., 2004).”
Transcriptional Regulation by Nrf2 (2017, background): “In response to oxidative stress, Keap1 is oxidized at reactive cysteine residues, resulting in Keap1 inactivation, Nrf2 stabilization and translocation into the nucleus (10, 32, 61, 92).”
Molecular Mechanisms of Nrf2-Mediated Antioxidant Response (2009, background): “the basal repressive activities on Nrf2 signaling [26,34,54].”
The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. (2013, background): “There is also conflicting evidence on the mechanism by which Nrf2 becomes free in the cell, some stating that electrophiles cause the dissociation of the Keap1–Nrf2 complex [39,40] whilst others suggest that the electrophiles cause the dissociation of Cul3 from Keap1 thus preventing the proteasomal ”
Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. (2006, background): “Keap1 contains critical -SH groups susceptible to oxidation, suggesting that release of Nrf2 by Keap1 is potentially under redox control (143, 374, 613).”