モノ対ポリユビキチネーション:Mdm2によるp53運命の差分制御

Muyang Li¹, Christopher L Brooks, Foon Wu-Baer

¹Institute for Cancer Genetics and Department of Pathology, College of Physicians & Surgeons, Columbia University, 1150 St. Nicholas Avenue, New York, NY 10032, USA.

Science (New York, N.Y.)

|December 13, 2003

まとめ

Mdm2タンパク質レベルはp53の運命を左右する. 低Mdm2の活動はp53の核輸出を引き起こし,高いMdm2はp53の分解を促し,その普遍性を明らかにする.

科学分野:

細胞生物学細胞生物学
分子生物学は分子生物学である.
バイオケミストリーバイオケミストリー

背景:

Mdm2媒介のユビキチネーションは,腫瘍抑制剤p53.3の安定性と局所化を調節するために重要である.
Mdm2がp53を分解するか,核の輸出かを決定する正確な分子機構は,完全に理解されていません.

研究の目的:

p53のユビキチネーションとサブセルラー局所化の調節におけるMdm2活性レベルの異なる役割を解明する.
p53の密輸と劣化に対するp53のモノウビキチネーションとポリウビキチネーションの特定の影響を調査する.

主な方法:

異なるMdm2活性レベル下でのp53のユビキチン化状態の分析.
p53のサブセルラー局所化とそのユビキチン化された形態の調査.
モノウビキチネーションを模倣するためにp53-ウビキチンの融合タンパク質を使用する.

主要な成果:

低Mdm2活性レベルは,p53のモノウビキチネーションと,その後の核輸出をもたらす.
高いMdm2活性レベルは,p53のポリユビキチン化と核内の分解につながります.
モノウビキチン化を模倣するp53-ウビキチン融合タンパク質は,Mdm2.から独立して細胞質に蓄積する.

結論:

p53 monoubiquitinationは,その細胞質の密輸を決定する重要な決定因子です.
異なるMdm2活性レベルは,p53の運命を制御する,異なるユビキチネーション経路をオーケストラします.
この研究は,p53の調節におけるユビキチネーションの役割を明らかにし,Mdm2の用量依存制御を強調しています.

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