p300のユビキチンリガース活性によるp53のポリユビキキチン化
Steven R Grossman1, Maria E Deato, Chrystelle Brignone
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Science (New York, N.Y.)
|April 12, 2003
まとめ
腫瘍抑制タンパク質p53は,分解のためにMDM2およびp300ユビキチンリガゼを必要とします. E1Aタンパク質はp300を阻害し,ポリユビキチン化されたp53を減少させ,プロテアソーム標的化に影響を与えます.
科学分野:
- 分子生物学は分子生物学である.
- 腫瘍学 腫瘍学
- タンパク質生化学 タンパク質生化学
背景:
- 腫瘍抑制タンパク質p53は,MDM2ユビキチンリガゼによって調節されるプロセスである急速なターンオーバーを経験します.
- p53とMDM2は,p300/CREB結合タンパク質の転写共同活性化剤と相互作用する.
- オンコタンパク質E1Aがp300に結合するとp53が安定し,p300がp53の分解に作用することを示唆する.
研究 の 目的:
- p53のユビキチン化と分解におけるp300の役割を調査する.
- p53の安定性を調節するp300,MDM2,E1Aの相互作用を解明する.
主な方法:
- 浄化されたp300とMDM2.2を用いたin vitroユビキチネーションアッセイ.
- E1A.を発現する細胞におけるp53のユビキチン化状態の分析.
- p300の固有のユビキチン・リガース活性とE1Aによる抑制の評価.
主要な成果:
- 浄化されたp300は,E1Aが抑制する固有ユビキチンリガゼ活性を示した.
- p300とMDM2が一緒にp53ポリユビキチネーションを in vitroで触媒化した.
- MDM2は単独でp53の単一ウビキチネーションを in vitroで触媒化した.
- 細胞におけるE1A発現は,ポリウビキチネートされたp53のレベルを低下させたが,モノウビキチネートされたp53は減少しなかった.
結論:
- MDM2とp300の両方のユビキチンリガゼ活動は,ポリユビキチン化p53.3を生成するために不可欠です.
- ポリユビキチネーションは,プロテアソーム媒介による分解のためにp53を標的とする.
- E1Aは,ポリユビキチン化におけるp300の役割を調節することにより,p53の分解に影響を与える.
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