日本語フィールド
著者：Suzuki, Takafumi; Muramatsu, Aki; Saito, Ryota; Iso, Tatsuro; Shibata, Takahiro; Kuwata, Keiko; Kawaguchi, Shin ichi; Iwawaki, Takao; Adachi, Saki; Suda, Hiromi; Morita, Masanobu; Uchida, Koji; Baird, Liam; Yamamoto, Masayuki題名：Molecular Mechanism of Cellular Oxidative Stress Sensing by Keap1発表情報：Cell Reports 巻: 28 号: 3 ページ: 746 - 758.e4キーワード：概要：© 2019 The Authors The Keap1-Nrf2 system plays a central role in the oxidative stress response; however, the identity of the reactive oxygen species sensor within Keap1 remains poorly understood. Here, we show that a Keap1 mutant lacking 11 cysteine residues retains the ability to target Nrf2 for degradation, but it is unable to respond to cysteine-reactive Nrf2 inducers. Of the 11 mutated cysteine residues, we find that 4 (Cys226/613/622/624) are important for sensing hydrogen peroxide. Our analyses of multiple mutant mice lines, complemented by MEFs expressing a series of Keap1 mutants, reveal that Keap1 uses the cysteine residues redundantly to set up an elaborate fail-safe mechanism in which specific combinations of these four cysteine residues can form a disulfide bond to sense hydrogen peroxide. This sensing mechanism is distinct from that used for electrophilic Nrf2 inducers, demonstrating that Keap1 is equipped with multiple cysteine-based sensors to detect various endogenous and exogenous stresses.抄録：英語フィールド
Author：Suzuki, Takafumi; Muramatsu, Aki; Saito, Ryota; Iso, Tatsuro; Shibata, Takahiro; Kuwata, Keiko; Kawaguchi, Shin ichi; Iwawaki, Takao; Adachi, Saki; Suda, Hiromi; Morita, Masanobu; Uchida, Koji; Baird, Liam; Yamamoto, MasayukiTitle：Molecular Mechanism of Cellular Oxidative Stress Sensing by Keap1Announcement information:Cell Reports Vol: 28 Issue: 3 Page: 746 - 758.e4An abstract：© 2019 The Authors The Keap1-Nrf2 system plays a central role in the oxidative stress response; however, the identity of the reactive oxygen species sensor within Keap1 remains poorly understood. Here, we show that a Keap1 mutant lacking 11 cysteine residues retains the ability to target Nrf2 for degradation, but it is unable to respond to cysteine-reactive Nrf2 inducers. Of the 11 mutated cysteine residues, we find that 4 (Cys226/613/622/624) are important for sensing hydrogen peroxide. Our analyses of multiple mutant mice lines, complemented by MEFs expressing a series of Keap1 mutants, reveal that Keap1 uses the cysteine residues redundantly to set up an elaborate fail-safe mechanism in which specific combinations of these four cysteine residues can form a disulfide bond to sense hydrogen peroxide. This sensing mechanism is distinct from that used for electrophilic Nrf2 inducers, demonstrating that Keap1 is equipped with multiple cysteine-based sensors to detect various endogenous and exogenous stresses.