Examination of coupled gene expression mechanisms of proteasome for anti-aging

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22826
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
• Research Institution: Doshisha University
• Principal Investigator: Kobayashi Akira 同志社大学, 生命医科学部, 教授 (50292214)
• Co-Investigator(Kenkyū-buntansha): 和久 剛 同志社大学, 生命医科学部, 助教 (40613584)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: タンパク質分解 / プロテアソーム / 転写因子 / 遺伝子発現

Outline of Final Research Achievements

We have analyzed and identified the following insights about the mechanism of protein homeostasis by the proteasome and the transcription factor NRF1 for development of anti-aging methods: (1) NRF1 regulates the gene expression of not only the proteasome but also the autophagy-related factors p62, TBK1, and GABARAPL1. Although the detailed mechanism of action is still under analysis, our observation suggests that NRF1 may also regulate protein homeostasis by autophagy. (2) We found that cancer cells shift from NRF1 to NRF1-related factor NRF3 for the regulation of proteasome expression. This finding suggests the existence of a new protein homeostasis mechanism regulated by NRF3.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

老化の要因は様々あるが、その１つに細胞内のタンパク質恒常性の破綻があげられる。したがってプロテアソームをはじめとするタンパク質恒常性維持メカニズムを解明し、その鍵となる分子を活性化する方法が開発できれば、エビデンスベースの新たなアンチエイジング戦略が可能になる。そのような観点からも、本研究の成果は、NRF1ないしNRF3による新たなタンパク質恒常性維持機構の発見という分子ないしメカニズムであるため、老化メカニズムの理解とその予防法の開発に対して重要な知見を与えると考える。