Molecular basis of the Keap1–Nrf2 system
TLDR
Cross talk between Nrf2 and other signaling pathways is identified, which provides new insights into the mechanisms by which the Keap1-Nrf2 system serves as a potent regulator of the authors' health and disease.About:
This article is published in Free Radical Biology and Medicine.The article was published on 2015-11-01 and is currently open access. It has received 688 citations till now. The article focuses on the topics: Ubiquitin ligase & Regulator.read more
Citations
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The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state
TL;DR: The aim of this review is to emphasize with current information the importance of antioxidants which play the role in cellular responce against oxidative/nitrosative stress, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue.
Journal ArticleDOI
Nrf2-Keap1 signaling in oxidative and reductive stress.
TL;DR: The effects of the Nrf2-Keap1 system in the physiology and pathophysiology of striated muscle tissue taking into account its role(s) in oxidative stress and reductive stress are highlighted.
Journal ArticleDOI
Ubiquitin Ligases: Structure, Function, and Regulation
Ning Zheng,Nitzan Shabek +1 more
TL;DR: Current progress in structure-function studies of ubiquitin ligases as well as exciting new discoveries of novel classes of E3s and diverse substrate recognition mechanisms are summarized.
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Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression
TL;DR: Genetic or pharmacological enhancement of NRF2 activity in the renal tubules significantly ameliorates damage related to AKI and prevents AKI progression to chronic kidney disease (CKD) by reducing oxidative stress.
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The Keap1-Nrf2-ARE Pathway As a Potential Preventive and Therapeutic Target: An Update.
TL;DR: The main focus of this review is on recent progress in studies of agents that target the Keap1–Nrf2–ARE pathway and the therapeutic applications of such agents.
References
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An nrf2/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements
Ken Itoh,Tomoki Chiba,Satoru Takahashi,Tetsuro Ishii,Kazuhiko Igarashi,Yasutake Katoh,Tatsuya Oyake,Norio Hayashi,Kimihiko Satoh,Ichiro Hatayama,Masayuki Yamamoto,Yo-ichi Nabeshima +11 more
TL;DR: It is demonstrated that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes and the nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.
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Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Ken Itoh,Nobunao Wakabayashi,Yasutake Katoh,Tetsuro Ishii,Kazuhiko Igarashi,James Douglas Engel,James Douglas Engel,Masayuki Yamamoto +7 more
TL;DR: It is postulate that Keap1 and Nrf2 constitute a crucial cellular sensor for oxidative stress, and together mediate a key step in the signaling pathway that leads to transcriptional activation by this novel NRF2 nuclear shuttling mechanism.
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The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1
Masaaki Komatsu,Hirofumi Kurokawa,Satoshi Waguri,Keiko Taguchi,Akira Kobayashi,Yoshinobu Ichimura,Yoshinobu Ichimura,Yu-shin Sou,Yu-shin Sou,Izumi Ueno,Ayako Sakamoto,Kit I. Tong,Mihee Kim,Yasumasa Nishito,Shun-ichiro Iemura,Tohru Natsume,Takashi Ueno,Eiki Kominami,Hozumi Motohashi,Keiji Tanaka,Masayuki Yamamoto +20 more
TL;DR: The findings indicate that the pathological process associated with p62 accumulation results in hyperactivation of Nrf2 and delineates unexpected roles of selective autophagy in controlling the transcription of cellular defence enzyme genes.
Journal ArticleDOI
Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2
Akira Kobayashi,Moon Il Kang,Hiromi Okawa,Makiko Ohtsuji,Yukari Zenke,Tomoki Chiba,Kazuhiko Igarashi,Masayuki Yamamoto +7 more
TL;DR: It is found that both the BTB and intervening-region (IVR) domains are crucial for Nrf2 degradation, implying that these two domains act to recruit ubiquitin-proteasome factors.
Journal ArticleDOI
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
Gina M. DeNicola,Florian A. Karreth,Timothy J. Humpton,Aarthi Gopinathan,Cong Wei,Kristopher K. Frese,Dipti Mangal,Kenneth H. Yu,Charles J. Yeo,Eric S. Calhoun,Francesca Scrimieri,Jordan M. Winter,Ralph H. Hruban,Christine A. Iacobuzio-Donahue,Scott E. Kern,Ian A. Blair,David A. Tuveson +16 more
TL;DR: Oncogene-directed increased expression of Nrf2 is a new mechanism for the activation of the NRF2 antioxidant program, and is evident in primary cells and tissues of mice expressing K-RasG12D and B-RafV619E, and in human pancreatic cancer.
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