Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival.
Mi Kyoung Kwak,Nobunao Wakabayashi,Nobunao Wakabayashi,Ken Itoh,Hozumi Motohashi,Masayuki Yamamoto,Thomas W. Kensler +6 more
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TLDR
Induction of nrf2-dependent genes involved in the recognition and repair/removal of damaged proteins expands the role of this pathway beyond primary control of electrophilic and oxidative stresses into secondary protective actions that enhance cell survival.About:
This article is published in Journal of Biological Chemistry.The article was published on 2003-03-07 and is currently open access. It has received 640 citations till now. The article focuses on the topics: Gene expression & Gene expression profiling.read more
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Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
TL;DR: The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway, and this review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses.
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Cancer chemoprevention with dietary phytochemicals
TL;DR: Attention has recently been focused on intracellular-signalling cascades as common molecular targets for various chemopreventive phytochemicals.
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Redox Regulation of Cell Survival
Dunyaporn Trachootham,Dunyaporn Trachootham,Dunyaporn Trachootham,Weiqin Lu,Marcia A. Ogasawara,Nilsa Rivera-Del Valle,Nilsa Rivera-Del Valle,Peng Huang +7 more
TL;DR: The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed and the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases.
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The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
TL;DR: Observations suggest Nrf2 directs metabolic reprogramming during stress, which would enable the factor to orchestrate adaptive responses to diverse forms of stress.
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Nrf2:INrf2 (Keap1) signaling in oxidative stress.
TL;DR: The switching on and off of Nrf2 protects cells against free radical damage, prevents apoptosis, and promotes cell survival, and is a mechanism of critical importance for cellular protection and cell survival.
References
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Book
Free radicals in biology and medicine
TL;DR: 1. Oxygen is a toxic gas - an introduction to oxygen toxicity and reactive species, and the chemistry of free radicals and related 'reactive species'
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The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
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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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Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants
Albena T. Dinkova-Kostova,W. David Holtzclaw,Robert N. Cole,Ken Itoh,Nobunao Wakabayashi,Yasutake Katoh,Masayuki Yamamoto,Paul Talalay +7 more
TL;DR: This finding suggests that reaction of cysteine thiols is followed by rapid formation of protein disulfide linkages, which are the direct sensors of inducers of the phase 2 system.