哺乳類のSrb/Mediator複合体は,アデノウイルスE1Aタンパク質の標的である
T G Boyer1, M E Martin, E Lees
1Molecular Biology Institute, UCLA, Los Angeles, California 90095-1570, USA.
Nature
|June 3, 1999
まとめ
アデノウイルスE1Aタンパク質は,SUR-2を含むヒトのメディエーター複合体と相互作用して,ウイルスの遺伝子転写を活性化します. この相互作用は,ウイルスの複製と細胞プロセスにとって極めて重要です.
科学分野:
- 分子生物学は分子生物学である.
- ウイルス学 ウイルス学 ウイルス学
- 細胞生物学 細胞生物学
背景:
- アデノウイルスE1Aタンパク質は,ウイルス複製に不可欠であり,細胞サイクル進行とウイルス転写を促進します.
- E1Aタンパク質は,RBやCBPのような細胞調節タンパク質と相互作用して,これらの効果を達成します.
研究 の 目的:
- E1A亜鉛指ドメインがウイルスの初期の遺伝子転写を活性化するメカニズムを調査する.
- E1A媒介による転写活性化に関与する宿主細胞因子を特定する.
主な方法:
- タンパク質とタンパク質の相互作用を研究するための生化学的測定法.
- 精製された成分を用いたインビトロ転写アッセイ.
- 酵母Srb/Mediatorタンパク質の同型を用いたタンパク質複合体の分析.
主要な成果:
- E1A亜鉛指ドメインは,酵母Srb/Mediatorタンパク質の同種を含む宿主細胞のマルチタンパク質複合体と結合する.
- この相互作用は,C. elegans SUR-2の同類であるヒトSUR-2との安定した結合を伴う.
- 特定されたヒトSrb/Mediator複合体は,E1AとVP16の活性化ドメインに反応して,体内での転写を刺激する.
- また,MAPキナーゼシグナル伝達によるETSファミリーの転写因子活性化には,ヒトSur-2の相互作用も必要である.
結論:
- E1A亜鉛指ドメインは,ヒトSUR-2を含む宿主細胞Srb/Mediator複合体を利用して,ウイルスの初期の遺伝子転写を活性化します.
- この発見は,ウイルスの転写制御のための新しいメカニズムを明らかにし,ウイルスのプロセスにおける保存された細胞機構の役割を強調しています.
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