Analysis of cell aging mechanisms through posttranslational modification-induced downregulation of proteasome activity

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06859
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Gunma Paz University
• Principal Investigator: Kimura Ayuko 群馬パース大学, 医療技術学部, 講師 (50553616)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: ユビキチン / 細胞老化 / プロテオミクス

Outline of Final Research Achievements

In current analysis, authors analyzed the posttranslational modifications on proteasome subunits and changes in ubiquitin proteome using model cell lines of cell aging to reveal the mechanisms underlying cell senescence and aging-related diseases. Western blot and in-gel activity assay of proteasome indicated the significant decrease of proteasome activity and increase of polyubiquitinated proteins in aged cell lines. Ubiquitin proteome analysis also revealed the upregulation of enzymes involved in protein ubiquitination, proteins involved in age-related disorder, and ubiquitination of membrane proteins involved in apoptosis in aged cell line. In addition, western blot and immunocytochemistry analyses showed the increase of K63-linked ubiquitin and altered intracellular localizations of K48- and K63-linked ubiquitins.

Free Research Field

プロテオミクス

Academic Significance and Societal Importance of the Research Achievements

プロテアソーム活性の増減が細胞の老化や寿命、がん化に関わることは以前から報告されていたが、本研究ではその生理的意義について、細胞内ユビキチン化タンパク質の比較プロテオーム解析手法を用いて初めて明らかにすることができた。今回の解析で、老化モデル細胞特異的な増加が見られる種々のユビキチン化タンパク質が明らかにされたことにより、老化や老化関連疾患の分子機構解明が進み、深刻化の懸念される超高齢社会に伴う医療問題の解決の糸口となることが期待される。