論文 - 詳細
| RRC ID | 57611 |
|---|---|
| 著者 | Suzuki T, Muramatsu A, Saito R, Iso T, Shibata T, Kuwata K, Kawaguchi SI, Iwawaki T, Adachi S, Suda H, Morita M, Uchida K, Baird L, Yamamoto M. |
| タイトル | Molecular Mechanism of Cellular Oxidative Stress Sensing by Keap1. |
| ジャーナル | Cell Rep |
| Abstract |
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. |
| 巻・号 | 28(3) |
| ページ | 746-758.e4 |
| 公開日 | 2019-7-16 |
| DOI | 10.1016/j.celrep.2019.06.047 |
| PII | S2211-1247(19)30820-4 |
| PMID | 31315052 |
| MeSH | Animals Cysteine / metabolism* HEK293 Cells Humans Hydrogen Peroxide / metabolism* Kelch-Like ECH-Associated Protein 1 / chemistry Kelch-Like ECH-Associated Protein 1 / genetics* Kelch-Like ECH-Associated Protein 1 / metabolism* Mice Mice, Inbred C57BL Mice, Knockout Mutation NF-E2 Transcription Factor / genetics NF-E2 Transcription Factor / metabolism Oxidative Stress / genetics* Oxidative Stress / physiology |
| IF | 7.815 |
| 引用数 | 17 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 28 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC05704 |