Opposing functions of ATF2 and Fos-like transcription factors in e-Jun-mediated myogenin expression and terminal differentiation of avian myoblasts
Opposing functions of ATF2 and Fos-like transcription factors in e-Jun-mediated myogenin expression and terminal differentiation of avian myoblasts
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DOI：
10.1038/sj.onc.1204967
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发表时间：
2001-11-29
期刊：
影响因子：
8
通讯作者：
Cabello, G
中科院分区：
文献类型：
--
作者：
Daury, L;Busson, M;Cabello, G
为了确定c-jun对成肌细胞的影响，我们进行了c-jun和/或ATF2、Fra2、c-Fos过表达的稳定转染实验。在诱导分化之前，c-jun抑制成肌细胞退出细胞周期，TPA处理也是如此。然而，与TPA不同的是，去除血清后，c-jun显著刺激成肌细胞分化。在寻找参与这种双重影响的特定合作伙伴时，我们发现c-Fos和Fra2的数量减少，c-jun蛋白的增加发生在细胞融合处，这种情况可能有利于c-jun和ATF2在末端分化过程中的合作。C-Fos和FRA2与c-Jun协同作用使成肌细胞退出细胞周期和终末分化，而ATF2的共同表达增强了e-Jun对肌源性细胞的正向影响。此外，肌生成素的表达是这种合作的积极靶点，这种调节是通过刺激肌生成素启动子的活性来实现的：(1)虽然c-Fos或Fra2共表达抑制了c-jun对该启动子的刺激活性，但ATF2共表达增强了这种影响；(2)使用显性负ATF2突变体，我们建立了c-jun转录活性需要内源ATF2功能的结论。这些数据表明，c-jun通过与不同合作伙伴的合作所产生的这种双重的肌源性影响，参与了成肌细胞增殖持续时间的控制以及随后的融合效率的控制。
With the aim to identify the oncoprotein partners implicated in the c-Jun myogenic influence, we carried out stable transfection experiments of c-Jun and/or ATF2, Fra2, c-Fos overexpression in avian myoblasts. Before induction of differentiation, c-Jun repressed myoblast withdrawal from the cell cycle, as did a TPA treatment. However, after serum removal, unlike TPA, c-Jun significantly stimulated myoblast differentiation. In search for specific partners involved in this dual influence, we found that a reduction in the amounts of c-Fos and Fra2 and an increase in c-Jun proteins occurred at cell confluence, a situation likely to favor cooperation between c-Jun and ATF2 during terminal differentiation. Whereas c-Fos and Fra2 cooperated with c-Jun to abrogate myoblast withdrawal from the cell cycle and terminal differentiation, ATF2 co-expression potentiated the positive myogenic e-Jun influence. In addition, myogenin expression was a positive target of this cooperation and this regulation occurred through a stimulation of myogenin promoter activity: (1) whereas c-Fos or Fra2 co-expression abrogated c-Jun stimulatory activity on this promoter, ATF2 co-expression potentiated this influence; (2) using a dominant negative ATF2 mutant, we established that c-Jun transcriptional activity required functionality of endogenous ATF2. These data suggest that through this dual myogenic influence due to cooperations with different partners, c-Jun is involved in the control of duration of myoblast proliferation and thereafter of fusion efficiency.