プロテアソーム媒介によるDef1の処理は,転写ストレスに対する細胞応答の重要なステップです
Marcus D Wilson1, Michelle Harreman1, Michael Taschner1
1Mechanisms of Transcription Laboratory, Clare Hall Laboratories, Cancer Research UK London Research Institute, South Mimms EN6 3LD, UK.
Cell
|September 3, 2013
まとめ
DNA損傷は,Def1.1経由でRNAポリメラーゼII (RNAPII) の分解を誘発する. Def1は処理によって活性化され,RNAPIIポリユビキチル化とタンパク質分解のためのE3リガースの核蓄積と徴募につながります.
科学分野:
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
- 遺伝学 遺伝学とは
背景:
- DNAの損傷により,A型が活性化されます.
- 最後の手段のメカニズム
- RNAポリメラーゼII (RNAPII) の最大のサブユニットのポリユビキチル化と分解を伴う.
- イーストでは,このプロセスはDef1タンパク質に依存しているが,正確なメカニズムは不明のままである.
研究 の 目的:
- Def1が転写ストレス中にRNAPIIの分解を容易にする以前の未解明のメカニズムを解明する.
- DNA損傷に対する反応として,Def1の活性化と機能について詳しく説明します.
主な方法:
- Ubiquitylationとプロテアソーム依存処理によるDef1の活性化を調査した.
- 処理されたDef1とRNAPIIの局所化と相互作用を分析した.
- Def1.1によるElongin-Cullin E3リガゼ複合体の徴募を特徴づけた.
主要な成果:
- Def1の活性化には,ユビキティレーションとプロテアソームに依存した処理が含まれており,サイトプラズマの局所化ドメインが除去されます.
- 処理されたDef1は核に蓄積され,RNAPII.と結合する.
- Def1は,そのユビキチン結合ドメインを利用して,Ela1経由でElongin-Cullin E3リガゼ複合体を募集し,Rpb1のポリユビキチル化を促進します.
結論:
- Def1は,転写ストレスに対する反応として,エルンギン・カリン・ユビキチン・リゲーゼの活性に対する重要なファシリテーターとして作用する.
- Def1が介在するRpb1のポリユビキチル化と分解のための多段階メカニズムが概説されています.
- Def1処理は,その核の局所化と,RNAPIIの分解を誘発する後の機能に不可欠です.
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