The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1

By M. Komatsu, H. Kurokawa, S. Waguri, K. Taguchi, A. Kobayashi, Yoshinobu Ichimura, Yu-shin Sou, Izumi Ueno, A. Sakamoto, K. I. Tong and 9 more. Nature Cell Biology, 2010

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Subfields: Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e33690ad2edb54f3b0412fac7cbf3dd2847cd324

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Citations in the corpus

Autophagy and the integrated stress response (2010, positive): “Moreover, as noted below, the phosphorylation of eIF2a (Kouroku et al., 2007; Talloczy et al., 2002) and the activation of IKK (Criollo et al.”
Nrf2, the Master Regulator of Anti-Oxidative Responses (2017, background): “p62/SQSTM1 comp tes with Nrf2 for binding to Keap1, thereby leading to decreased degradation of Nrf2 and increased activity [28,107,108].”
Activation of the p62-Keap1-NRF2 Pathway Protects against Ferroptosis in Hepatocellular Carcinoma Cells (2015, background): “Recently, studies have demonstrated that the substrate adaptor p62 (also called sequestosome-1) protein modulates NRF2 expression levels by directly interacting with Keap1 under stressors, including liver damage.(29) Based on this, we next examined the effects of p62 on the regulation of NRF2 expres”
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (2012, neutral): “dant response pathway through a KEAP1 binding domain.(428,429) In fact, SQSTM1 may, itself, be transcriptionally induced by NFE2L2.”
Transcriptional Regulation by Nrf2 (2017, background): “When autophagy is impaired, p62 levels are elevated, leading to degradation of Keap1 and consequent Nrf2 stabilization (26, 83, 90).”
The cytoprotective role of the Keap1–Nrf2 pathway (2011, background): “In addition to Nrf2, Keap1 has also been shown to bind to other proteins, including IKKb, p62, and PGAM5 (Lo and Hannink 2006a; Lo and Hannink 2008; Lee et al. 2009; Komatsu et al. 2010; Lau et al. 2010; Jain et al. 2010; Kim et al. 2010).”
p62 links autophagy and Nrf2 signaling. (2015, background): “Subsequently, several reports confirmed the accumulation of Nrf2 in the liver as being due to p62-mediated Keap1 inactivation, which in turn triggered liver damage, inflammation, fibrosis, and tumorigenesis [18,28,35,61,63,68].”
Antioxidant responses and cellular adjustments to oxidative stress (2015, background): “For example, some proteins, such as autophagy substrate p62 and p53regulated p21, interfere with the Keap1-dependent ubiquitination of Nrf2 by disrupting Nrf2-Keap1 binding causing persistent activation of Nrf2 [56,57].”
NRF2, a Transcription Factor for Stress Response and Beyond (2020, background): “More importantly, autophagy deficiency leads to accumulation of p62, a multifunctional cargo receptor that can sequester KEAP1 and stabilize NRF2, resulting in NRF2 activation [10].”
Recent insights into the function of autophagy in cancer (2016, background): “Accumulation of p62 also promotes lung and mammary tumorigenesis induced by autophagy deficiency (Moscat and Diaz-Meco 2012; Wei et al. 2014). p62 activates NRF2 by binding to its inhibitor, KEAP1 (Komatsu et al. 2010; Lau et al. 2013), and also activates mTOR and NFκB as discussed above, and its ab”
Autophagy and aging. (2011, background): “CR and resveratrol induce Enhanced inflammation, steatohepatitis, enhanced frequency of hepatocellular carcinomas, lung adenocarcinomas, and lymphomas in aging mice; enhanced accumulation of intraneuronal amyloid ß upon transgenic expression of human amyloid precursor protein Aging-related malignanc”
A Noncanonical Mechanism of Nrf2 Activation by Autophagy Deficiency: Direct Interaction between Keap1 and p62 (2010, background): “5a, the double-knockout mice had milder p62 accumulation than the excessive accumulation of p62 in Atg7 single-knockout mice (7).”