反対の展開タンパク質応答信号は,アポトーシスを制御するために死亡受容体5に収束します
Min Lu1, David A Lawrence1, Scot Marsters1
1Cancer Immunology, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Science (New York, N.Y.)
|July 5, 2014
まとめ
エンドプラズマ網膜 (ER) のストレスが展開タンパク質応答 (UPR) を引き起こす. 持続的なUPRは死亡受容体5 (DR5) を活性化し,アポトーシスを誘発し,ERのストレスを細胞死と関連付けます.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- 生理学 生理学とは
背景:
- エンドプラズマ網膜 (ER) のタンパク質の折り畳みは,細胞機能にとって不可欠です.
- ERのストレスはタンパク質の折り畳みを妨害し,病気につながります.
- 展開タンパク質応答 (UPR) は,ERホメオスタシスを回復しようとします.
研究 の 目的:
- 持続的なERストレスがアポプトティック細胞死を誘発するメカニズムを解明する.
- ERストレス誘発アポトーシスにおける死亡受容体5 (DR5) の役割を調査する.
主な方法:
- DR5規制におけるUPRメディエーターであるCHOPとIRE1αの役割を調査した.
- ERストレス下でのDR5転写とmRNA崩壊のダイナミクスを分析した.
- リガンド独立DR5の活性化とカスパース8の結合を検証した.
主要な成果:
- 緩和されていないERのストレスは,UPR制御DR5.5経由で細胞自律アポトーシスを活性化させる.
- CHOPはDR5の転写を介し,IRE1αはDR5mRNAを一時的に分解する.
- 持続的なERストレスは,細胞内DR5タンパク質の蓄積につながり,アポトーシスを引き起こします.
結論:
- DR5は,持続的なERストレスへの反応としてアポトーシスの重要な媒介者として作用します.
- UPRは反対の信号を統合してDR5発現と細胞運命を制御します.
- DR5の活性化は,ERのストレスをプログラムされた細胞死経路に結びつける.
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