Suzuki Takafumi, Yamamoto Masayuki
From the Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
From the Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
J Biol Chem. 2017 Oct 13;292(41):16817-16824. doi: 10.1074/jbc.R117.800169. Epub 2017 Aug 24.
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.
转录因子Nrf2（NF-E2相关因子2）是细胞应对环境应激反应的主要调节因子。Nrf2诱导解毒和抗氧化酶的表达，并抑制促炎细胞因子基因的诱导。Keap1（类Kelch ECH相关蛋白1）是基于Cullin 3的E3泛素连接酶的衔接子亚基。Keap1调节Nrf2的活性，并作为氧化应激和亲电应激的传感器。在本综述中，我们讨论了Keap1-Nrf2系统感知和调节细胞对环境应激反应的分子机制。特别地，我们重点关注Keap1的多种应激感知机制和Nrf2的新调节功能。
