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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\u2010like modifier (SUMO)\u2010mediated 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\u2010specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA\u2010binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co\u2010activator yes\u2010associated protein 1 in the Hippo pathway. Finally, adeno\u2010associated virus serotype 9 is used to construct TEAD1 wild\u2010type 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\u2010related heart failure.<\/jats:p>","DOI":"10.1002\/advs.202305677","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:17:59Z","timestamp":1705364279000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["SUMOylation of TEAD1 Modulates the Mechanism of Pathological Cardiac Hypertrophy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9260-7584","authenticated-orcid":false,"given":"Xin","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine  Shanghai 200030 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuening","family":"Dang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular 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