Cell cycle-regulated expression of the muscle determination factor Myf5 in proliferating myoblasts
Cell cycle-regulated expression of the muscle determination factor Myf5 in proliferating myoblasts
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DOI：
10.1083/jcb.140.1.111
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发表时间：
1998-01-12
影响因子：
7.8
通讯作者：
Pinset, C
中科院分区：
文献类型：
--
作者：
Lindon, C;Montarras, D;Pinset, C
Myf5是已知最早在体内表达的肌肉特异性因子，其表达与成肌细胞谱系的确定相关。在 C2 细胞中，我们通过免疫细胞定位显示 Myf5 从已启动分化程序的细胞中迅速消失。在增殖的成肌细胞中，各个细胞检测到的 Myf5 和 MyoD 水平非常不均匀。我们发现 Myf5 表达的一些异质性源于细胞周期对 Myf5 的转录后调节。对同步培养物提取物的免疫印迹显示，Myf5 在细胞周期中经历周期性波动，并且在使用诺考达唑阻断早期有丝分裂的细胞中不存在。有丝分裂细胞中 Myf5 的消失涉及细胞周期这一阶段特有的 Myf5 磷酸化形式的蛋白水解降解。相比之下，有丝分裂 C2 细胞中的 MyoD 水平并未耗尽。Myf5 的有丝分裂破坏是转录因子的第一个例子显示细胞周期调节的降解，考虑到 Myf5 在维持增殖细胞的测定和分化开始计时方面的可能作用，这些结果可能很重要。
Myf5 is the earliest-known muscle-specific factor to be expressed in vivo and its expression is associated with determination of the myoblast lineage. In C2 cells, we show by immunocytolocalization that Myf5 disappears rapidly from cells in which the differentiation program has been initiated. In proliferating myoblasts, the levels of Myf5 and MyoD detected from cell to cell are very heterogeneous. We find that some of the heterogeneity of Myf5 expression arises from a posttranscriptional regulation of Myf5 by the cell cycle. Immunoblotting of extracts from synchronized cultures reveals that Myf5 undergoes periodic fluctuations during the cell cycle and is absent from cells blocked early in mitosis by use of nocodazole, The disappearance of Myf5 from mitotic cells involves proteolytic degradation of a phosphorylated form of Myf5 specific to this phase of the cell cycle, In contrast, MyoD levels are not depleted in mitotic C2 cells, The mitotic destruction of Myf5 is the first example of a transcription factor showing cell cycle-regulated degradation, These results may be significant in view of the possible role of Myf5 in maintaining the determination of proliferating cells and in timing the onset of differentiation.