Elucidation of a novel homeostatic mechanism by enhanced O-GlcNAcylation under proteasome dysfunction

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07062
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Hamazaki Jun 東京大学, 大学院薬学系研究科(薬学部), 助教 (80533588)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: プロテアソーム / ユビキチン / O-GlcNAc

Outline of Final Research Achievements

The 26S proteasome is a protein complex that plays a role in protein degradation and plays an essential role in all eukaryotic cells. We identified that the enhanced O-GlcNAcylation of proteins is important to cellular proteostasis under proteasome dysfunction. In this study, we investigated the role and physiological importance of novel factors identified by mass spectrometry or genetic explorations to elucidate the molecular mechanism of O-GlcNAcylation. We identified the novel factor that act on the regulation of proteasome function and clarify their function of them, but there is a need for detailed verification and further development of research.

Free Research Field

タンパク質分解

Academic Significance and Societal Importance of the Research Achievements

哺乳類プロテアソームの機能制御や生理機能についてはまだ未解明の部分が多く、プロテアソーム機能不全が関与すると考える広範な病態発症の基本原理の理解には課題が多いのが現状である。本研究においてプロテアソーム不全時にどのような細胞応答が生じるかを明らかにし、それを担う新たなプロテアソーム制御因子の同定と機能解明を進めたことは学術的にも重要性は高く、治療アプローチの作用点として今後研究が発展することで応用研究の基盤としても将来性が高い。