異なったp53転写プログラムが,急性DNA損傷反応と腫瘍抑制を決定する

Colleen A Brady¹, Dadi Jiang, Stephano S Mello

¹Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Cell

|May 14, 2011

まとめ

腫瘍抑制タンパク質p53はがん予防に不可欠ですが,そのメカニズムは不明です. この研究では,p53がp53であることを明らかにしました.

科学分野:

分子生物学は分子生物学である.
がん研究がん研究
遺伝学遺伝学とは

背景:

p53媒介による腫瘍抑制の基礎となる正確な分子機構は,完全に理解されていません.
p53は,DNA損傷に対する細胞の反応に関与する重要な腫瘍抑制タンパク質です.

研究の目的:

腫瘍抑制とDNA損傷応答におけるp53の独特の転写プログラムを解明する.
ノッキンマウスモデルを使用して,老化と腫瘍抑制におけるp53トランザクティベーションの役割を調査する.

主な方法:

一連のp53転写活性化変異体を発現するノックインマウスを利用した.
遺伝子トランザクティベーションを評価するためにマイクロアレイ分析を行った.
評価されたp53変異性の活性がG(1) 停止,アポトーシス,衰老,および腫瘍抑制に起因する.

主要な成果:

A p53変異体 (p53・25・26) は,ほとんどの標的遺伝子のトランザクティベーションが損なわれ,G・1) 停止/アポトーシスの障害を示した.
驚くべきことに,p53 ((25,26) は老化と腫瘍抑制における有意な活性を維持した.
トランザクティベーションデッドの変異体 (p53 ((25,26,53,54)) は,すべての老化と腫瘍抑制能力を失った.

結論:

既知のp53標的の大部分の効率的なトランザクティベーションは,老化と腫瘍抑制のために必要とされません.
p53のトランザクティベーションは,新しい標的遺伝子の独特のセットを通じて作用し,腫瘍抑制に不可欠です.
これらの発見は,p53がDNA損傷反応と腫瘍抑制における役割を区別し,治療の開発を支援しています.

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