Oxidative and Electrophilic Stresses Activate Nrf2 through Inhibition of Ubiquitination Activity of Keap1

By A. Kobayashi, Moon-Il Kang, Y. Watai, K. I. Tong, T. Shibata, K. Uchida, Masayuki Yamamoto. Molecular and Cellular Biology, 2006

909 citations recorded by the source corpus.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/05d90c2d38494c40c7e0b90e562a27be669854db

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Citations in the corpus

Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential (2009, background): “In this case, Nrf2 may not be released by Keap1, but rather, Nrf2 synthesized de novo would fail to bind Keap1 and would not be degraded [83-85] (Fig.”
The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1 (2010, background): “Exposure to electrophiles, reactive oxygen species and nitric oxide instigates the modification of the cysteine residues of Keap1, leading to its inactivatio”
Small Molecule Modulators of Keap1-Nrf2-ARE Pathway as Potential Preventive and Therapeutic Agents (2012, background): “Carnosol (54) and its acid derivative, carnosic acid (55) are catechol-type abietane diterpenes from Rosmarinus officinalis (rosemary).”
Keap1 Recruits Neh2 through Binding to ETGE and DLG Motifs: Characterization of the Two-Site Molecular Recognition Model (2006, background): “Indeed, treatment with chemical inducers did not discourage the association of Nrf2 to Keap1 but liberated Nrf2 from the Keap1-dependent polyubiquitination and proteasomal degradation (31).”
Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy (2008, methodology): “Immunoprecipitation, immunoblotting, and immunofluorescent analyses were performed as described (7, 8) with slight modifications.”
The Antioxidant Defense System Keap1-Nrf2 Comprises a Multiple Sensing Mechanism for Responding to a Wide Range of Chemical Compounds (2008, background): “Although detailed mapping of the 15d-PGJ2-sensor site has not yet been carried out, we assume that it is located within the Keap1 protein, since direct binding between 15d-PGJ2 and Keap1 has been demonstrated in cultured cells by us and others (11, 21, 25).”
Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism (2016, background): “Keap1, as a thiol-rich protein, possesses at least 27 reactive cysteines that can be modified by electrophiles what leads to Keap1 inactivation and Nrf2 stabilization [8].”
The cytoprotective role of the Keap1–Nrf2 pathway (2011, background): “The increased activity of Nrf2 in the presence of C273S/A or C288S/A mutant Keap1 was caused by reduced ubiquitination of Nrf2, and not by the dissociation of Keap1 from Nrf2 or Cullin 3 (Cul3) (Kobayashi et al. 2004, 2006; Zhang et al. 2004).”
Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders (2010, neutral): “Under basal conditions the pathway operates at low levels due to the repressor function of the cytosolic protein Keap1, which binds to the E3 ubiquitin ligase Cullin3-RING box1 and presents Nrf2 for ubiquitination and subsequent proteosomal degradation (200, 236, 324).”
Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution (2011, background): “Important observations related to this mechanism are that, even when Keap1–Cul3 E3 ligase activity is lost because of the challenge of electrophilic reagents, the overall interaction between Keap1 and Nrf2 is not disrupted (Kobayashi et al. 2006).”
Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. (2009, background): “As a consequence, Nrf2 protein levels are increased, and the Nrf2 signaling pathway is activated (Itoh et al., 1999; Kobayashi et al., 2004, 2006; McMahon et al., 2003; Zhang and Hannink, 2003; Zhang et al., 2004). p21 Cip1/WAF1 regulates many cellular processes such as cellcycle arrest, DNA…”
Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022, background): “On the other hand, the Keap1-Nrf2 association may remain intact via the tight-binding ETGE motif even though ubiquitination is impaired without DLG binding [56,58].”
Activation of Nrf2-antioxidant signaling attenuates NF-κB-inflammatory response and elicits apoptosis (2008, background): “[12] Kobayashi A, Kang MI, Watai Y, Tong KI, Shibata T, Uchida K, et al.”
Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis (2016, background): “Because Nrf2 is constantly degraded by the proteasomal activity of Keap1, the inhibition of Keap1 can activate the Nrf2-ARE pathway upon oxidative and electrophilic stresses [42].”