SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy

• Published in: Advanced science Vol. 11; no. 12; pp. e2305677 - n/a
• Main Authors: Shi, Xin, Dang, Xuening, Huang, Zhenyu, Lu, Yanqiao, Tong, Huan, Liang, Feng, Zhuang, Fei, Li, Yi, Cai, Zhaohua, Huo, Huanhuan, Jiang, Zhaolei, Pan, Changqing, Wang, Xia, Gu, Chang, He, Ben
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01-03-2024; John Wiley and Sons Inc; Wiley
• Subjects: cardiac hypertrophy; Cardiomyocytes; Cardiomyopathy; Heart failure; Localization; Oxidative stress; post‐translational modification; Protein expression; Proteins; SUMOylation; TEA domain transcription factor 1; SUMOylation; cardiac hypertrophy; oxidative stress; TEA domain transcription factor 1; post‐translational modification
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202305677

Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin‐like modifier (SUMO)‐mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO‐specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA‐binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co‐activator yes‐associated protein 1 in the Hippo pathway. Finally, adeno‐associated virus serotype 9 is used to construct TEAD1 wild‐type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy‐related heart failure.
Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. This study discovers that TEAD1 is an important transcription factor that plays a key regulatory role in cardiac hypertrophy. SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy‐related heart failure. Mechanistically, Nrf2‐Hmox1 is a potential target of oxidative stress in cardiac hypertrophy induced by the SUMOylation of TEAD1.