アセチル化はp53の活性化に不可欠です

Yi Tang¹, Wenhui Zhao, Yue Chen

¹Institute for Cancer Genetics, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.

Cell

|May 20, 2008

まとめ

腫瘍抑制剤p53のアセチル化は,その活性化に不可欠であり,細胞のストレス反応を可能にします. この変異はp53-Mdm2の相互作用を不安定化し,成長停止とアポトーシスを促進する.

科学分野:

分子生物学は分子生物学である.
細胞のストレス反応は,
腫瘍を抑制する.

背景:

腫瘍抑制剤p53は,遺伝子毒性ストレスに対する細胞の反応に不可欠です.
p53の活性化には,その阻害剤Mdm2.2との相互作用の破壊が必要です.
リン酸化やアセチル化のようなp53の翻訳後の改変がp53の活性化に果たす正確な役割については,まだ議論が続いている.

研究の目的:

p53.3 の主要なアセチル化部位をすべて特定する.
p53アセチル化がp53の活性化と機能に不可欠かどうかを判断する.
p53アセチル化がp53-Mdm2相互作用に影響を与えるメカニズムを解明する.

主な方法:

p53アセチル化部位を特定する.
アセチル化の有無でp53依存の成長停止とアポトーシスの分析.
p53対応のプロモーターにMdm2の採用に関する調査.

主要な成果:

p53アセチル化の喪失は,p53依存の成長停止とアポトーシスを完全に廃止しました.
p53のアセチル化により,Mdm2がターゲットプロモーターに勧誘されるのを防ぐことで,Mdm2媒介の抑制を無効化する.
アセチル化によるp53活性化は,そのリン酸化状態とは独立して発生する.

結論:

p53アセチル化は,p53媒介のストレス反応にとって不可欠な出来事です.
アセチル化はp53-Mdm2の相互作用を不安定化し,p53の活性化につながります.
この研究は,細胞のストレス反応経路におけるp53アセチル化の重要な役割を明らかにしています.

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