Elucidation of the mechanism of PLN degradation by Parkin

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07130
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Osaka Medical and Pharmaceutical University
• Principal Investigator: Shunichi Yokoe 大阪医科薬科大学, 医学部, 助教 (40454756)
• Co-Investigator(Kenkyū-buntansha): 朝日 通雄 大阪医科薬科大学, 医学部, 教授 (10397614)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ユビキチンリガーゼ / 心不全

Outline of Final Research Achievements

In human heart failure, increased ubiquitination of many proteins is observed. In this study, we found that phospholamban (PLN), a regulator of calcium pump (SERCA2a), is
downregulated by ubiquitin ligase "Parkin" in heart failure. In the hearts of various heart failure model mice, the binding between Parkin and PLN was significantly increased compared to wild-type mice. Furthermore, it was observed that the binding of PLN and PINK1, which are known to work in cooperation with Parkin, is also significantly increased. In conclusion, we suggest that Parkin plays a pivotal role in the degradation of PLN in heart failure.

Free Research Field

循環薬理学

Academic Significance and Societal Importance of the Research Achievements

日本では急速に高齢化が進み、心不全を始めとした心疾患の増加にも直面している。今回、心臓の律動的な拍動に重要な働きを担っている分子であるPLNに着目し、その分解に関与しているユビキチンリガーゼの探索を試みたところ、ParkinがPLNのユビキチン化および分解の一旦を担っていることを明らかにできた。将来的にParkinを標的とした治療戦略を立てることを目標としており、心不全症状の改善や治療法の向上を目指す上でとても意義があると考えられる。