Enhanced desumoylation in murine hearts by overexpressed SENP2 leads to congenital heart defects and cardiac dysfunction.

摘要: Sumoylation is a posttranslational modification implicated in variety of cellular activities, and its role number human pathogeneses such as cleft lip/palate has been well documented. However, the importance SUMO conjugation pathway cardiac development functional disorders newly emerging. We previously reported that knockout SUMO-1 mice led to congenital heart diseases (CHDs). To further investigate effects imbalanced on function underlying mechanisms, we generated transgenic (Tg) with cardiac-specific expression SENP2, SUMO-specific protease deconjugates sumoylated proteins, evaluate impact desumoylation function. Overexpression SENP2 resulted premature death CHDs-atrial septal defects (ASDs) and/or ventricular (VSDs). Immunobiochemistry revealed diminished cardiomyocyte proliferation SENP2-Tg mouse hearts compared wild type (WT) hearts. Surviving showed growth retardation, developed cardiomyopathy impaired aging. Cardiac-specific overexpression transgene reduced incidence structural phenotypes sumoylation defective mice. Moreover, Nkx2.5 haploinsufficiency promoted embryonic lethality severity CHDs, indicating interaction between vivo. Our findings indicate indispensability balanced for proper This article part Special Issue entitled 'Post-translational Modification SI'.