SCF/β-TrCP Promotes Glycogen Synthase Kinase 3-Dependent Degradation of the Nrf2 Transcription Factor in a Keap1-Independent Manner

By P. Rada, A. I. Rojo, S. Chowdhry, Michael T. McMahon, J. Hayes, A. Cuadrado. Molecular and Cellular Biology, 2011

729 citations recorded by the source corpus.

View Paper: https://www.semanticscholar.org/paper/9b103332ec17714912bb4fb3a1946133b599ef1f

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Citations in the corpus

Role of nrf2 in oxidative stress and toxicity. (2013, background): “β-TrCP is an adaptor protein for the Cul1-dependent SCF E3 and thereby promotes the ubiquitination and proteasomal degradation of Nrf2 independently of Keap1 (73).”
The cytoprotective role of the Keap1–Nrf2 pathway (2011, background): “Recent work suggests that GSK3b and the E3 ubiquitin ligase b-TRCP regulate the activity of the Neh6 degron in a Keap1-independent manner (Rada et al. 2011).”
Nrf2, the Master Regulator of Anti-Oxidative Responses (2017, background): “Neh2 and Neh6 are degrons, which allow Nrf2 targeting to proteasomal degradation by Keap1 (Kelch-like ECH-associated protein1) and β-TrCP (β-transducin repeats-containing proteins) [3].”
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): “Antonio Cuadrado and colleagues first showed that GSK-3β inhibits Nrf2 activity, but identification of the sites in Nrf2 that are phosphorylated by GSK-3 was achieved several years later using two-dimensional electrophoresis and mass spectrometry [75, 76, 299, 300].”
The emerging role of the Nrf2–Keap1 signaling pathway in cancer (2013, background): “Phosphorylation of the DSGIS motif by GSK-3 increases the ability of β-TrCP to ubiquitinate Nrf2 and promote its rapid turnover (McMahon et al. 2004; Rada et al. 2011; Chowdhry et al. 2013).”
Hydrogen peroxide sensing, signaling and regulation of transcription factors (2014, background): “Active GSK-3 catalyzes the phosphorylation of NRF2 in the Neh6 domain, forming a phosphodegron that is recognized by the substrate receptor transducin repeat-containing protein (-TrCP) complex, followed by NRF2 ubiquitination and degradation [211].”
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, methodology): “GSK-3 activity antagonises Nrf2 (25), and this has been postulated to entail the formation of a phosphodegron that is recognised by β-TrCP (28).”