Analysis of the regulation mechanism of CHK1 by Mule during myocardial stress response

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08410
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: TAKEDA Kenji 金沢医科大学, 総合医学研究所, 助教 (90340009)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ユビキチン / Mule / CHK1

Outline of Final Research Achievements

This study aimed to elucidate the degradation mechanism of CHK1 protein, which is crucial for the oxidative stress response in cardiomyocytes. After birth, cardiomyocytes stop dividing and are exposed to oxidative stress, with CHK1 playing a pivotal role in this process. CHK1 is regulated by an E3 ligase called Mule. Our research analyzed how Mule specifically recognizes and ubiquitinates CHK1 for degradation. As a result, we identified new pathways related to CHK1 degradation and clarified the roles of CHK1 and Mule in the glycation stress response. This work contributes to understanding the molecular mechanisms underlying cardiomyocyte stress responses and suggests potential targets for treating heart disease.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、心筋細胞の酸化ストレス応答におけるCHK1とMuleの相互作用メカニズムを明らかにした点にある。特に、糖化ストレスがCHK1の分解に与える影響を解析し、新たな経路を同定することで、心疾患治療の新しいターゲットを提案することができた。社会的意義としては、心筋細胞のストレス応答を理解することで、糖尿病性心疾患などの予防や治療に役立つ知見を提供する点である。