Opposite roles of MRF4 and MyoD in cell proliferation and myogenic differentiation
Opposite roles of MRF4 and MyoD in cell proliferation and myogenic differentiation
复制标题
DOI：
10.1016/j.bbrc.2007.10.042
复制
发表时间：
2007-12-21
影响因子：
3.1
通讯作者：
Whang, Kwang Youn
中科院分区：
文献类型：
--
作者：
Jin, Xun;Kim, Jong-Gun;Whang, Kwang Youn
基本的螺旋-环-螺旋生肌调节因子在骨骼肌发生中起着关键作用。在生肌调节因子(MRF)中，MRF4在肌瘤形成过程中呈现双相表达模式，但其功能尚不清楚。在这项研究中，我们使用BEF(自发永生化的牛胚胎成纤维细胞，通过MyoD的过度表达显示肌源性分化)和C2Cl2细胞来研究MRF4的功能。异位表达MRF4不能刺激BEF和C2Cl2细胞向肌细胞分化，但可显著促进BEF和C2Cl2细胞的增殖，上调细胞周期蛋白E，下调p21(WAFI)的表达。此外，MRF4还可以诱导作为p21(WAFI)转录激活剂的MyoD蛋白的降解，从而表明MRF4通过抑制MyoD依赖的p21(WAFI)的表达来加速细胞增殖。然而，在MRF4过表达的细胞中强制表达MyoD抑制了细胞的增殖并部分诱导了成肌细胞分化，这表明MyoD在细胞周期调控中可能是MRF4的负干扰因子。综上所述，这些结果表明，MRF4和MyoD分别通过刺激细胞增殖和分化在肌肉发生中发挥竞争作用。(C)2007 Elsevier Inc.保留所有权利。
The basic helix-loop-helix myogenic regulatory factors play critical roles in skeletal myogenesis. Among the myogenic regulatory factors (MRFs), MRF4 shows a biphasic expression pattern during the formation of myotomes, although its function remains unclear. In this study, we used BEF (spontaneously immortalized bovine embryonic fibroblast that shows myogenic differentiation by overexpression of MyoD) and C2Cl2 cells to investigate the function of MRF4. Ectopic expressions of MRF4 did not stimulate myogenic differentiation in the BEF and C2Cl2 cells, but did show a marked increase of cell proliferation, upregulation of cyclin E, and downregulation of p21(WAFI). Furthermore, MRF4 was found to induce degradation of the MyoD protein, which acts as a transcriptional activator for p21(WAFI), and thus indicates that MRF4 accelerates cell proliferation by suppressing MyoD-dependent p21(WAFI) expression. However, forced expression of MyoD in the MRF4-overexpressing cells inhibited cell proliferation and partially induced myogenic differentiation, which suggests that MyoD is a potential negative intercessor of MRF4 in the regulation of the cell cycle. Taken together, these results indicate that MRF4 and MyoD play competitive roles in myogenesis by stimulating cell proliferation and differentiation, respectively. (C) 2007 Elsevier Inc. All rights reserved.