E1Aオンコタンパク質によって標的にされるトランスクリプションアダプタータンパク質の一族

Z Arany¹, D Newsome, E Oldread

¹Dana Farber Cancer Institute, Boston, Massachusetts.

Nature

|March 2, 1995

まとめ

アデノウイルスE1Aオンコタンパク質は,転写アダプタタンパク質であるp300とCBPを標的とする. E1Aはp300を抑制する.

科学分野:

分子生物学は分子生物学である.
細胞生物学細胞生物学
ウイルス学ウイルス学ウイルス学

背景:

p300タンパク質は細胞サイクル,強化剤,分化を調節する.
CBPタンパク質はCREB転写因子と循環型AMP誘発プロモーターを同活性化します.
p300 と CBP は非常に似たシーケンスを共有しています.

研究の目的:

p300,CBP,およびアデノウイルスE1A.の機能的関係を調査する.
E1Aがp300とCBPの転写活動を阻害するかどうかを判断する.
E1AとCBPの間のインビボ相互作用を調査する.

主な方法:

p300による転写刺激の評価.
p300の活性に対するE1Aの抑制効果を試験する.
DNAに結合したCREBファミリーメンバーとのCBPの関連性を調査する.
E1AとCBPの相互作用を in vivoで検証する.

主要な成果:

p300は転写を刺激し,この活動は特にE1Aによって抑制されます.
CBPは,CREBファミリーのメンバーとDNA結合複合体を形成します.
E1AとCBPは,in vivoで相互作用する.
E1Aは,cAMP依存の転写を抑制し,CBPの機能的ターゲティングを示しています.

結論:

p300とCBPは,トランスクリプションアダプタータンパク質の一族を構成しています.
アデノウイルスE1Aオンコタンパク質は,特にこのp300/CBPタンパク質ファミリーをターゲットとしています.
E1AがCBPと相互作用し,転写活動の阻害がウイルス腫瘍生成の重要なメカニズムである.

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