The role of HECT-Type Ubiquitin E3 Ligase HECW2 for pathological cardiac hypertrophy

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20890
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Yamagata University
• Principal Investigator: Goto Jun 山形大学, 医学部, 客員研究員 (70810836)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: HECW2 / 心肥大 / ユビキチン / E3リガーゼ

Outline of Final Research Achievements

As the population ages, the number of heart failure patients is increasing, creating a worldwide problem known as the heart failure pandemic. Pathological cardiac hypertrophy is a major cause of heart failure, but its mechanism is not fully understood. Recently, many studies have reported the association between HECT-type ubiquitin E3 ligase and cardiac diseases. HECW2 is a HECT-type ubiquitin E3 ligase belonging to the NEDD4 family, but
the relationship between HECW and the cardiac hypertrophy and heart failure has not been fully investigated. In this study, we investigate the role of HECW2 in the development of cardiac hypertrophy using cardiomyocytes. Furthermore, we generate cardiac-specific HECW-overexpressing transgenic mice and examine cardiac tissue, protein, and survival in heart failure model induced by Thoracic transverse aortic constriction.

Free Research Field

循環器

Academic Significance and Societal Importance of the Research Achievements

心不全は増加傾向にある日本人の重要な死因である。心不全では、病的心肥大が生じるが、その機序は十分には解明されていない。ユビキチン化による標的タンパク質の翻訳後修飾は、タンパク質の機能調節や分解において重要な役割を担う（Nat Med.2014;20:1242-53.）。HECW2はNEDD4ファミリーに属するHECT型ユビキチン転移酵素である。近年、HECT型ユビキチン転移酵素と心疾患との関連が報告されているが、心臓におけるHECW2の機能についての報告はない。病的心肥大発症におけるHECW2の研究を行うことで、新たな病的心肥大の機序やHECW2の機能解明につながる可能性がある。