Distinct Cysteine Residues in Keap1 Are Required for Keap1-Dependent Ubiquitination of Nrf2 and for Stabilization of Nrf2 by Chemopreventive Agents and Oxidative Stress

By Donna D. Zhang, Mark Hannink. Molecular and Cellular Biology, 2003

1,420 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/1659aff9efd22e1dc4e96f1eb3b2dbe8271a018a

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In Molecular Biology

Citations in the corpus

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).”
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): “Within the IVR domain of Keap1, Cys-273 and Cys-288 are essential for the turnover of Nrf2 in vitro and in vivo, with mutation of either of these residues resulting in the loss of Nrf2 ubiquitination by Keap1 [250, 268].”
SCF/β-TrCP Promotes Glycogen Synthase Kinase 3-Dependent Degradation of the Nrf2 Transcription Factor in a Keap1-Independent Manner (2011, background): “The Keap1-Cul3-Rbx1 complex is able to ubiquitinate Nrf2 and target it for proteasomal degradation only under normal redox conditions, and upon exposure to oxidants or electrophiles, Cys-151, Cys-273, and Cys-288 in Keap1 become modified, leading to disturbance of the interaction between Nrf2 and Ke”
Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders (2010, neutral): “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).”
Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2 (2004, background): “Recently, it was reported that mutation of Cys273 to Ser reduced Keap1-dependent ubiquitination of Nrf2, resulting in the stabilization of Nrf2 (31).”
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).”
Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. (2009, background): “…for homodimerization, the linker domain contains several cysteine residues that sense intracellular redox imbalance, and the Kelch domain binds the N-terminal Neh2 domain of Nrf2 (Itoh et al., 1999; Wakabayashi et al., 2004; Yamamoto et al., 2008; Zhang and Hannink, 2003; Zipper and Mulcahy, 2002).”