Journal ArticleDOI
Nrf2-Keap1 defines a physiologically important stress response mechanism.
Reads0
Chats0
TLDR
Analysis of keap1-knockout mice provides solid evidence that Keap1 acts as a negative regulator of Nrf2 and as a sensor of xenobiotic and oxidative stresses.About:
This article is published in Trends in Molecular Medicine.The article was published on 2004-11-01. It has received 1529 citations till now. The article focuses on the topics: KEAP1 & Transcription factor.read more
Citations
More filters
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
Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications.
TL;DR: The molecular and biochemical characterization of HOs is reviewed, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by environmental stress, to lay a foundation for potential future clinical applications of these systems.
Journal ArticleDOI
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
Selective autophagy mediated by autophagic adapter proteins
Terje Johansen,Trond Lamark +1 more
TL;DR: The mechanistic basis of selective autophagy in mammalian cells discussing the degradation of misfolded proteins, p62 bodies, aggresomes, mitochondria and invading bacteria is reviewed and the emerging picture of selectivity affecting the regulation of cell signaling with consequences for oxidative stress responses, tumorigenesis and innate immunity is addressed.
Journal ArticleDOI
Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism
TL;DR: This review summarizes knowledge about Nrf2 and HO-1 across different phyla suggesting their conservative role as stress-protective and anti-aging factors.
References
More filters
Journal ArticleDOI
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.
Journal ArticleDOI
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.
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
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.
Journal ArticleDOI
The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity.
TL;DR: The data suggest that the sequence, 5'-puGTGACNNNGC-3' 3'-pyCACTGNNNCG-5' where N is any nucleotide, represents the core sequence of the ARE required for transcriptional activation by phenolic antioxidants and metabolizable planar aromatic compounds.