Inhibition of in vitro myogenic differentiation by cellular transcription factor E2F1.
Inhibition of in vitro myogenic differentiation by cellular transcription factor E2F1.
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发表时间：
1995-10
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通讯作者：
J. Wang;K. Helin;P. Jin;B. Nadal-Ginard
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作者：
J. Wang;K. Helin;P. Jin;B. Nadal-Ginard
培养的心肌细胞的终末分化需要细胞退出细胞周期。成肌细胞中几种癌基因的结构性过表达可以抑制体外的肌肉发生。在这里，我们研究了细胞转录因子E2F1在成肌分化中的作用。在C2C12细胞分化过程中，E2F1的表达不可逆地下调。此外，C2C12细胞中E2F1表达的失控阻止了肌源性分化。这种对肌肉生成的抑制与抑制肌生成蛋白的表达和上调细胞周期蛋白D1的表达有关。此外，在分化条件下，过表达E2F1的心肌细胞不能退出细胞周期。这些结果与E2F1可以作为癌基因发挥作用的观点一致，并进一步表明E2F1下调是肌源性分化所必需的。
Terminal differentiation of cultured myocytes requires withdrawal of the cells from the cell cycle. Constitutive overexpression of several oncogenes in myoblasts can inhibit in vitro myogenesis. Here we studied the role of the cellular transcription factor E2F1 on myogenic differentiation. E2F1 expression is irreversibly down-regulated during differentiation of C2C12 myocytes. Furthermore, deregulated E2F1 expression in C2C12 cells prevented myogenic differentiation. This inhibition of myogenesis was associated with the repression of myogenin expression and an elevated cyclin D1 expression. Moreover, E2F1-overexpressing myocytes failed to exit the cell cycle under differentiation conditions. These results are consistent with the notion that E2F1 can function as an oncogene and further suggest that E2F1 down-regulation is required for myogenic differentiation.