Journal ArticleDOI
Regulatory Mechanisms Controlling Gene Expression Mediated by the Antioxidant Response Element
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TLDR
This review focuses on the molecular mechanisms whereby the transcriptional activation mediated by the interaction between the ARE and NF-E2-related factor 2 (Nrf2) is regulated.Abstract:
The expression of genes encoding antioxidative and Phase II detoxification enzymes is induced in cells exposed to electrophilic compounds and phenolic antioxidants. Induction of these enzymes is regulated at the transcriptional level and is mediated by a specific enhancer, the antioxidant response element or ARE, found in the promoter of the enzyme's gene. The transcription factor Nrf2 has been implicated as the central protein that interacts with the ARE to activate gene transcription constitutively or in response to an oxidative stress signal. This review focuses on the molecular mechanisms whereby the trancriptional activation mediated by the interaction between the ARE and NF-E2-related factor 2 (Nrf2) is regulated. Recent studies suggest that the sequence context of the ARE, the nature of the chemical inducers, and the cell type are important for determining the activity of the enhancer in a particular gene.read more
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Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
TL;DR: This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival, ROS homeostasis and antioxidant gene regulation, mitochondrial oxidative stress, apoptosis, and aging.
Journal ArticleDOI
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.
Journal ArticleDOI
Role of nrf2 in oxidative stress and toxicity.
TL;DR: The nuclear factor erythroid 2-related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants that controls the basal and induced expression of an array of antioxidant response element-dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure.
Journal ArticleDOI
The mammalian unfolded protein response
TL;DR: In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into their native conformation and undergo posttranslational modifications important for their activity and structure as mentioned in this paper.
Journal ArticleDOI
The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress
TL;DR: A possible role of the Nrf2-antioxidant response element transcriptional pathway in neuroprotection and the nature of this pathway and the mechanisms by which Keap1 acts to repress NRF2 activity are the topics of discussion in this minireview.
References
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Journal ArticleDOI
Specificity and mechanism of action of some commonly used protein kinase inhibitors
TL;DR: The results demonstrate that the specificities of protein kinase inhibitors cannot be assessed simply by studying their effect on kinases that are closely related in primary structure, and proposes guidelines for the use of protein Kinase inhibitors in cell-based assays.
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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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Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1.
Masao Saitoh,Hideki Nishitoh,Makiko Fujii,Kohsuke Takeda,Kei Tobiume,Yasuhiro Sawada,Masahiro Kawabata,Kohei Miyazono,Hidenori Ichijo +8 more
TL;DR: Evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine‐ and stress‐induced apoptosis.
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Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways
Alan J. Whitmarsh,Roger J. Davis +1 more
TL;DR: Recent progress towards understanding AP-1 regulation by the ERK, JNK, and p38 MAP kinase signal transduction pathways is reviewed.