TY - JOUR
T1 - Stress-sensing mechanisms and the physiological roles of the Keap1–Nrf2 system during cellular stress
AU - Suzuki, Takafumi
AU - Yamamoto, Masayuki
N1 - Funding Information:
This work was supported in part by MEXT/JSPS KAKENHI Grants 26111002 (to M. Y.) and 17K15590 and 26111010 (to T. S.), AMED-P-CREATE (to M. Y.), the Naito Foundation (to M. Y.), the Takeda Science Foundation (to M. Y.), and the Platform Project for Support in Drug Discovery and Life Science Research (Platform for Drug Discovery, Informatics, and Structural Life Sci-ence) from the Ministry of Education, Culture, Sports, Science and Technol-ogy (MEXT) and Japan Agency for Medical Research and Development (AMED) (to M. Y.). This is the third article in the Thematic Minireview series “Redox metabolism and signaling.” The authors declare that they have no conflicts of interest with the contents of this article.
Publisher Copyright:
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2017/10/13
Y1 - 2017/10/13
N2 - Transcription factor Nrf2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. Nrf2 induces the expression of detoxification and antioxidant enzymes and suppresses the induction of pro-inflammatory cytokine genes. Keap1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of Cullin 3-based E3 ubiquitin ligase. Keap1 regulates the activity of Nrf2 and acts as a sensor for oxidative and electrophilic stresses. In this review, we discuss the molecular mechanisms by which the Keap1–Nrf2 system senses and regulates the cellular response to environmental stresses. In particular, we focus on the multiple stress-sensing mechanisms of Keap1 and novel regulatory functions of Nrf2.
AB - Transcription factor Nrf2 (NF-E2-related factor 2) is a master regulator of cellular responses against environmental stresses. Nrf2 induces the expression of detoxification and antioxidant enzymes and suppresses the induction of pro-inflammatory cytokine genes. Keap1 (Kelch-like ECH-associated protein 1) is an adaptor subunit of Cullin 3-based E3 ubiquitin ligase. Keap1 regulates the activity of Nrf2 and acts as a sensor for oxidative and electrophilic stresses. In this review, we discuss the molecular mechanisms by which the Keap1–Nrf2 system senses and regulates the cellular response to environmental stresses. In particular, we focus on the multiple stress-sensing mechanisms of Keap1 and novel regulatory functions of Nrf2.
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U2 - 10.1074/jbc.R117.800169
DO - 10.1074/jbc.R117.800169
M3 - Short survey
C2 - 28842501
AN - SCOPUS:85031305447
SN - 0021-9258
VL - 292
SP - 16817
EP - 16824
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 41
ER -