E4F1は非典型のユビキチンリガゼで,p53エフェクタルの機能を降解から独立して調節する

Laurent Le Cam¹, Laëtitia K Linares, Conception Paul

¹Institut de Génétique Moléculaire CNRS-UMII UMR5535, IFR122, Montpellier 34293, France. llecam@igmm.cnrs.fr

Cell

|November 18, 2006

まとめ

E4F1は,p53を改変する新しいユビキチンE3リガゼです. この規則はp53に影響を与える.

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
バイオケミストリーバイオケミストリー

背景:

p53タンパク質の活動は,翻訳後の改変によって厳しく調節されます.
Hdm2媒介のユビキチレーションは,タンパク質分解のためにp53を標的にします.
E4F1は,以前にウイルスオンコタンパク質E1Aの標的として特定された亜鉛指タンパク質です.

研究の目的:

p53.3の新たなレギュレータを特定する.
p53の翻訳後の改変と機能におけるE4F1の役割を特徴付けるために.
E4F1媒介による改変がp53の細胞運命を決定する役割にどのように影響するか解明する.

主な方法:

同免疫プレシピテーションは,p53に関連した因子を特定するための測定法です.
Ubiquitination assaysは,E4F1.1.によるp53変異を検出するための測定法である.
染色体免疫降水 (ChIP) は,p53-染色体関連性を評価する.
P53依存遺伝子発現を分析するための転写プロファイリング.

主要な成果:

E4F1は,Hdm2.2と異なるp53に対する非典型のユビキチンE3リガゼとして機能する.
E4F1は,p53のヒンドル領域の特定のライシン残基のオリゴ-ユビキチテレーションを媒介する.
E4F1に依存したp53の全域存在化はクロマチンと関連しており,アポトーシスではなく,細胞サイクル停止を促進する.
p53のE4F1とPCAF媒介による改変は,互いを排斥しています.

結論:

E4F1は,p53.5の重要な翻訳後の調節体である.
E4F1はp53エフェクター機能を調節し,細胞を成長停止に導く.
この発見は,p53を媒介する細胞の運命決定を制御する新しいメカニズムを明らかにしています.

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