pVHLは,ユビキチン独立のタンパク質分解によってTCF/LEF転写因子のタンパク質の安定性を調節する

Caixia Wang^1,2, Xiaozhi Rong^3,4, Haifeng Zhang^1,2

¹Key Laboratory of Marine Drugs (Ocean University of China), Chinese Ministry of Education, and School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.

Cellular and molecular life sciences : CMLS

|September 4, 2025

まとめ

フォン・ヒッペル・リンダウタンパク質 (pVHL) は,新しいユビキチン独立タンパク質経路を通じて,Wnt/β-カテニンのシグナル伝達に不可欠なTCF/LEF転写因子を直接分解する.

科学分野:

分子生物学
細胞生物学
発達生物学

背景:

Wnt/β-catenin経路は細胞の増殖と運命を調節する.
TCF/LEFの転写因子は,Wntの信号伝達の主要なメディエーターである.
TCF/LEFタンパク質の安定性を制御するメカニズムは十分に理解されていません.

研究の目的:

TCF/LEFのタンパク質の安定性を研究する.
Wnt/β-カタニン経路の新たなレギュレータを特定する.
TCF/LEFの規制におけるpVHLの役割を調査する.

主な方法:

培養細胞とゼブラフィッシュをモデルシステムとして利用した.
pVHLとTCF/LEFのタンパク質相互作用を調査した.
評価されたタンパク質分解経路
ゼブラフィッシュの遺伝子ノックアウト研究を行いました

主要な成果:

pVHLはTCF/LEFタンパク質に直接結合する.
pVHLは,E3リガース活性とは独立してTCF/LEFのタンパク質分解を促進する.
pVHLのホモログであるpVHLLもTCF/LEFのレベルを低下させる.
ゼブラフィッシュのVHLノックアウトは,背面ヘブンニューロンの発達に影響します.

結論:

pVHLは,ユビキチンに依存しないメカニズムを通じてTCF/LEFの安定性を調節する.
pVHLは26Sプロテアソーム結合ドメインを分解する.
この研究は,Wnt/β-カテニンのシグナル伝達のための新しい規制メカニズムを明らかにしています.

キーワード:

脊髄神経細胞 TCF/LEF ユビキチン独立のプロテアソマル分解 Wnt/β-カタニンシグナリング pVHL について

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