Elucidation of Cancer-Promoting Mechanisms Through mTORC1-Dependent Regulation of Liquid-Liquid Phase Separation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07155
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Nagoya City University
• Principal Investigator: Nakatsumi Hirokazu 名古屋市立大学, 医薬学総合研究院(薬学), 准教授 (20596837)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: mTORC1 / P-body / Translation

Outline of Final Research Achievements

In this study, we identified that the liquid-liquid phase separation of P-bodies is regulated by the phosphorylation enzyme mTORC1. Results from ribosome profiling and proteome analysis revealed that mTORC1 promotes the translation of mRNAs localized in P-bodies. While it was previously known that mTORC1 controls translation by targeting ribosomal proteins, the regulation discovered in this study targets different mRNAs and is independent of the known signaling pathways. Although P-bodies have been known to function in translational repression, our research indicates that the formation of P-bodies functions to promote the translation of specific groups of mRNAs.

Free Research Field

シグナル伝達

Academic Significance and Societal Importance of the Research Achievements

mTORC1の異常活性化はがんをはじめとした様々な疾患を増悪させる。mTORC1の阻害剤であるラパマイシンは抗がん剤として既に使用されているが、未だ改善の余地を残している。mTORC1の分子機能の詳細を解明することは、関連疾患の治療法の開発や、ラパマイシンの副作用の低減に寄与しうる。本研究ではこれらの分子機能の一端を明らかにし、タンパク質合成に関連した新たな制御機構を明らかにした。