title: A novel Fbxo25 acts as an E3 ligase for destructing cardiac specific transcription factors.
abstract: Alterations in ubiquitin-proteasome system (UPS) have been implicated in the etiology of human cardiovascular diseases. Skp1/Cul1/F-box (SCF) ubiquitin E3 ligase complex plays a pivotal role in ubiquitination of cardiac proteins. However, a specific ubiquitin E3 ligase responsible for the destruction of cardiac transcription factors such as Nkx2-5, Isl1, Mef2C, and Tbx5 remains elusive to date. Here, we show that a novel F-box containing Fbxo25 is cardiac-specific and acts as an ubiquitin E3 ligase for cardiac transcription factors. Fbxo25 expression was nuclei-specific in vitro and cardiomyocytes. Expression level of Fbxo25 was higher in a fetal heart than an adult. Moreover, Fbxo25 expression was increased along with those of cardiac-specific genes during cardiomyocyte development from ESCs. Fbxo25 expression facilitated protein degradation of Nkx2-5, Isl1, Hand1, and Mef2C. Especially, Fbxo25 ubiquitinated Nkx2-5, Isl1, and Hand1. Altogether, Fbxo25 acts as an ubiquitin E3 ligase to target cardiac transcription factors including Nkx2-5, Isl1, and Hand1, indicating that cardiac protein homeostasis through Fbxo25 has a pivotal impact on cardiac development.
authors: Stem Cell Research Laboratory, Department of Developmental Biology, CHA University, Seoul 135-907, Republic of Korea.
authors: Jae-Woo
authors: JW
authors: Jang
authors: Won-Young
authors: WY
authors: Lee
authors: Jae-Ho
authors: JH
authors: Lee
authors: Sung-Hwan
authors: SH
authors: Moon
authors: Chang-Hoon
authors: CH
authors: Kim
authors: Hyung-Min
authors: HM
authors: Chung