A novel Fbxo25 acts as an E3 ligase for destructing cardiac specific transcription factors

► Fbxo25 expression is higher in a fetal heart than that of an adult and is nuclei-specific in mouse and human cardiomyocytes. ► It increases along with those of cardiac-specific genes during differentiation from ESCs. ► It facilitates protein degradation of Nkx2-5, Isl1, Hand1, and Mef2C. ► These degradations are promoted by ubiquitination depending on Fbxo25. ► Thus, Fbxo25-mediated UPS has a pivotal impact on cardiac development.