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J Biol Chem. 2017 Oct 13;292(41):16817-16824. doi: 10.1074/jbc.R117.800169. Epub 2017 Aug 24.

Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2 system during cellular stress.

Author information

1
From the Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
2
From the Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan masiyamamoto@med.tohoku.ac.jp.

Abstract

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.

KEYWORDS:

Keap1; animal model; anti-inflammation; antioxidant; gene regulation; nuclear factor 2 (erythroid-derived 2-like factor) (NFE2L2) (Nrf2); stress response

PMID:
28842501
PMCID:
PMC5641889
DOI:
10.1074/jbc.R117.800169
[Indexed for MEDLINE]
Free PMC Article

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