SUMO-specific protease 2 governs cardiac function through the regulation of β-catenin SUMOylation

Cardiovascular Disease (CVD) is one of the most common diseases caused by a variety of factors, with high morbidity and mortality. In this discourse, it is revealed that SUMO-specific Protease 2-conditional knockout (CKO) in cardiomyocytes causes hypertrophy and fibrosis, leading to myocardial cardiac dysfunction. Further results demonstrated that β-catenin expression was significantly elevated, and phosphorylated β-catenin was reduced in SUMO-specific Protease 2 CKO mice and knockdown cells. The stability of β-catenin is regulated by a SUMO-dependent ubiquitin-mediated proteolytic cascade. SUMOylation promoted the nuclear import of β-catenin and upregulated the expression levels of its targeted Transcription Factors. Furthermore, the expression level of SUMO-specific Protease 2 was decreased, whereas β-catenin was increased in the serum of patients with Heart Failure. More importantly, suppression of the Wnt/β-catenin signaling pathway significantly improved cardiac function in SUMO-specific Protease 2 CKO mice. This revelation improves our understanding of the pivotal role of SUMO-specific Protease 2 in the orchestration of β-catenin SUMOylation, indicating the critical role of the SUMO-specific Protease 2-β-catenin axis in the maintenance of cardiac function.