National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
FEBS J. 2010 Jan;277(2):466-76. doi: 10.1111/j.1742-4658.2009.07498.x. Epub 2009 Dec 15.
The ubiquitin ligase RING finger protein 13 gene (RNF13) was first identified in a screen for genes whose expression is regulated by myostatin in chicken fetal myoblasts. In this study, we demonstrate that the RNF13 gene is broadly expressed in many chicken tissues. The expression of RNF13 gradually decreases during skeletal myogenesis, and myostatin up-regulates RNF13 expression at both the transcriptional and translational levels. Interestingly, ectopic expression of RNF13 inhibits cell proliferation and suppresses the expression of the myogenic genes MyoD and Caveolin-3 in muscle cells. Moreover, recently, we have reported that RNF13 is a RING-type E3 ubiquitin ligase. In this report, we provide experimental evidence to show that mutations disrupting the RING finger abolish the growth-suppressive activity of RNF13, indicating that its E3 ligase activity is required for the inhibition of cell proliferation. Taken together, our findings show that RNF13 functions as an E3 ubiquitin ligase to negatively regulate cell proliferation.
泛素连接酶 RING 指蛋白 13 基因（RNF13）最初是在鸡胎儿成肌细胞中筛选受肌肉生长抑制素调控表达的基因时发现的。在本研究中，我们证明 RNF13 基因在许多鸡组织中广泛表达。RNF13 的表达在骨骼肌发生过程中逐渐降低，肌肉生长抑制素在转录和翻译水平上均上调 RNF13 的表达。有趣的是，RNF13 的异位表达抑制细胞增殖，并抑制肌肉细胞中肌源性基因 MyoD 和 Caveolin-3 的表达。此外，最近我们报道 RNF13 是一种 RING 型 E3 泛素连接酶。在本报告中，我们提供了实验证据表明，破坏 RING 指的突变会使 RNF13 的生长抑制活性丧失，表明其 E3 连接酶活性对于抑制细胞增殖是必需的。综上所述，我们的研究结果表明 RNF13 作为一种 E3 泛素连接酶，可负向调节细胞增殖。
