アルツハイマーや癌治療の手がかりとなるタンパク質代謝マッピング(Protein turnover mapping may offer clues for Alzheimer’s, cancer treatment)

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2025-03-20 イェール大学

イェール大学の研究者たちは、タンパク質の合成と分解の速度、すなわち「タンパク質のターンオーバー」をマッピングする新技術を開発しました。この手法により、アルツハイマー病やがんなどの疾患に関連する異常なタンパク質の動態を詳細に解析することが可能となり、新たな治療法の開発に役立つ可能性があります。

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マウス組織と脳領域にわたるプロテオームとリン酸化プロテオームのターンオーバーアトラス Turnover atlas of proteome and phosphoproteome across mouse tissues and brain regions

Wenxue Li ∙ Abhijit Dasgupta ∙ Ka Yang∙ … ∙ Eugenio F. Fornasiero ∙ Junmin Peng∙ Yansheng Liu
Cell  Published:March 20, 2025
DOI:https://doi.org/10.1016/j.cell.2025.02.021

Graphical abstract

アルツハイマーや癌治療の手がかりとなるタンパク質代謝マッピング(Protein turnover mapping may offer clues for Alzheimer’s, cancer treatment)

Highlights

  • A high-quality comprehensive resource of protein turnover across mouse tissues
  • Protein abundance and lifetime together define tissue proteome function and stability
  • Protein lifetime strongly correlates with protein-protein interactions in tissues
  • Site-specific phosphorylation functionally shapes in vivo protein lifetime

Summary

Understanding how proteins in different mammalian tissues are regulated is central to biology. Protein abundance, turnover, and post-translational modifications such as phosphorylation are key factors that determine tissue-specific proteome properties. However, these properties are challenging to study across tissues and remain poorly understood. Here, we present Turnover-PPT, a comprehensive resource mapping the abundance and lifetime of 11,000 proteins and 40,000 phosphosites in eight mouse tissues and various brain regions using advanced proteomics and stable isotope labeling. We reveal tissue-specific short- and long-lived proteins, strong correlations between interacting protein lifetimes, and distinct impacts of phosphorylation on protein turnover. Notably, we discover a remarkable pattern of turnover changes for peroxisome proteins in specific tissues and that phosphorylation regulates the stability of neurodegeneration-related proteins, such as Tau and α-synuclein. Thus, Turnover-PPT provides fundamental insights into protein stability, tissue dynamic proteotypes, and functional protein phosphorylation and is accessible via an interactive web-based portal at https://yslproteomics.shinyapps.io/tissuePPT.

医療・健康
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