ティオール過酸化酵素は,遺伝子活性化におけるH2O2受容体およびリドックストランスデューサーです
Agnès Delaunay1, Delphine Pflieger, Marie Bénédicte Barrault
1Laboratoire Stress Oxydants et Cancers, SBGM, DBJC, CEA-Saclay, 91191 Gif-sur-Yvette, Cedex, France.
Cell
|November 20, 2002
まとめ
グルタチオンペロキシダゼのような酵素Gpx3は,ヒドロペロキシドセンサーとして作用し,信号を細胞応答の調節のためのYap1転写因子に伝達します. これは,Gpx3とYap1.1.を巻き込んだ新しいエウカリオスの水酸化物感知機構を明らかにしています.
科学分野:
- * 細胞生物学について
- * バイオケミストリー
- * 分子生物学 * 分子生物学
背景:
- * 転写因子Yap1は,Saccharomyces cerevisiaeの水酸化物ホメオスタシスの維持に不可欠である.
- * Yap1の活性化は,細胞内の水酸化物濃度の上昇によって引き起こされるが,直接的な酸化機構は不明であった.
研究 の 目的:
- *ヒドロペロキシドがYap1転写因子を活性化するメカニズムの解明.
- * 水酸化物信号のセンサーとトランスデューサをYap1.1に識別する.
主な方法:
- *水酸化物,Gpx3,およびS. cerevisiaeにおけるYap1との相互作用を調査した.
- * 二酸化硫化物結合形成と解消を分析するために生化学的分析を用いた.
- * 経路の調節におけるチオレドキシンの役割を調べました.
主要な成果:
- *Yap1は,ヒドロペロキシドによって直接酸化されません.
- *グルタチオン過酸化酵素 (GPx) 類酵素Gpx3は,水酸化物センサーとして機能する.
- *Gpx3はYap1と分子間二硫化結合を形成し,Yap1では分子内結合に解消され,活性化を意味する.
- *チオレドキシンは,Gpx3とYap1.1の両方を減少させ,経路を無効化する.
結論:
- *Gpx3は,ヒドロペロキシド受容体とリドックストランスデューサーとして作用し,Yap1.1への信号伝送を媒介する.
- * この研究は,ヒドロペロキシドを感知し,それに反応する新しい真核生物のメカニズムを明らかにしています.
- *この発見は,GPxのような酵素が細胞の調節における酸化還元シグナリングの役割を強調しています.
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