セルリン1987での自己リン酸化は,ネズミのATM活性化 in vivoでは不要である

Manuela Pellegrini¹, Arkady Celeste, Simone Difilippantonio

¹Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1360, USA.

Nature

|August 15, 2006

まとめ

アタクシア・テランジエクタシア変異 (ATM) タンパク質は,

科学分野:

分子生物学は分子生物学である.
遺伝学遺伝学とは
細胞生物学細胞生物学

背景:

ATMタンパク質キナーゼの活性化は,DNA二重鎖破裂 (DSB) 修復に不可欠です.
ATM機能障害は,がんの予備性を含む深刻な健康問題につながる.
Ser 1987での自己リン酸化は,ATMが活性化していることの重要なマーカーです.

研究の目的:

ATMオートフォスフォリレーションが,ATM活性化におけるセル1987における役割を調査する.
ATM Ser 1987 リン酸化がATM機能に不可欠であるかどうかを判断する.
DNA損傷によるATM活性化の代替メカニズムを探求する.

主な方法:

Ser 1987 から Ala 変異型の Atm を発現するマウスを生成した.
これらのマウスのATM依存の細胞と生物の反応を評価した.
変異したATMタンパク質の支配的負の活性を評価した.

主要な成果:

変異したATM (Ser 1987 Ala) を有するマウスは,機能的なATM依存反応を示した.
変異したATMタンパク質は,支配的な負の効果を示さなかった.
これらの発見は,ATMのアクティベーションの確立されたモデルに挑戦しています.

結論:

Ser 1987でのATM自己リン酸化は,ATM活性化の原因ではなく,結果である可能性があります.
DNAの二重鎖の断裂は,ATMを別の経路で活性化させる可能性があります.
これは,DNA修復におけるATMシグナル伝達の理解を修正したことを示唆している.

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