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新しいヒトp53同型はATR-intra-Sフェーズチェックポイントの不可欠な要素です
Gabor Rohaly1, Jan Chemnitz, Silke Dehde
1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Martinistrasse 52, D-20251, Hamburg, Germany.
Cell
|July 13, 2005
まとめ
新たに特定されたp53同型体DeltaP53は,損傷したS相細胞の転写活性を示している. この腫瘍抑制アイソフォームはp21遺伝子を活性化させ,細胞サイクル進行とDNA修復に影響を与えます.
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
- がん研究 がん研究
背景:
- 腫瘍抑制タンパク質p53は,トランザクティベーション特性で知られています.
- 既存のヒトのp53イソフォームは,一般に転写的に不活性であると考えられています.
- DNA損傷反応におけるp53の役割は確立されています.
研究 の 目的:
- 新しいp53イソフォーム,DeltaP53.3の転写活性を調査する.
- Deltap53が独立したトランザクション機能を備えているかどうかを判断する.
- S相内チェックポイントにおける Deltap53 の役割を明らかにする.
主な方法:
- p53.3. 代替スプライシングの分析
- レポーターアッセイは,p53とDeltaP53によるプロモーターのトランザクティベーションを評価する.
- DNA損傷に対する反応として,細胞サイクル分析.
- タンパク質の発現と活性を検出するためのウェスタン・ブロッティング.
主要な成果:
- 代替的にスプライスされたp53イソフォームであるDeltaP53は,転写活性を示しています.
- Deltap53は,p53.3とは異なり,p21および14-3-3シグマプロモーターを選択的にトランザクティベーションします.
- Deltap53の活動は,損傷したS相細胞とATR-intra-S相チェックポイントに特異的です.
- Deltap53誘発のp21発現は,サイクリンA-Cdkの活性を下回し,S相進行を弱める.
結論:
- Deltap53は,転写的に活性な腫瘍抑制剤同型として機能する.
- Deltap53-p21-cyclin A-Cdk経路は,DNA修復と複製の解離に不可欠である.
- Deltap53はATR-intra-S相DNA損傷チェックポイントの重要な構成要素です.
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