Transcriptional and posttranscriptional control of c-myc during myogenesis: its mRNA remains inducible in differentiated cells and does not suppress the differentiated phenotype

Transcriptional and posttranscriptional control of c-myc during myogenesis: its mRNA remains inducible in differentiated cells and does not suppress the differentiated phenotype
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肌发生过程中 c-myc 的转录和转录后控制:其 mRNA 在分化细胞中保持可诱导状态,并且不会抑制分化表型

DOI:
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发表时间:
1986
影响因子:
5.3
通讯作者:
B. Nadal
B. Nadal
中科院分区:
生物学2区
文献类型:
--
作者:
T. Endo;B. Nadal

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人们普遍认为细胞癌基因c-myc在细胞增殖的控制中发挥重要作用,并且其表达在分化细胞中减少。我们通过使用大鼠骨骼肌细胞系 L6E9 的亚克隆来检查 c-myc 表达与细胞增殖或分化之间是否存在相关性。成肌细胞不可逆地退出细胞周期,融合形成多核肌管,并表达肌肉特异性基因(终末分化)。肌肉特异性基因也可以在没有融合(生化分化)的情况下表达。这种单核但生化分化的细胞可以被刺激重新进入细胞周期。 c-myc 由 G0 停滞细胞中的胰岛素、胰岛素样生长因子或血清因子诱导,而蛋白质合成抑制剂的诱导或蛋白质合成抑制剂与血清因子组合的超诱导发生在所有测试的生理状态中。我们发现c-myc表达在生化和终末分化细胞以及静止未分化细胞中降低,但在所有三种生理状态下它仍然可以被生长因子诱导。核径流转录测定的结果表明,生长因子对c-myc mRNA的诱导及其在这些生理状态下的去诱导主要在转录水平上受到调节。相反,单独的蛋白质合成抑制剂和与生长因子组合的c-myc mRNA的诱导和超诱导分别主要通过c-myc mRNA的稳定化进行转录后调节。此外,c-myc 和肌肉特异性基因可以在生化细胞和终末分化细胞中同时转录。这些结果表明,c-myc 的不可逆抑制对于终末肌原性分化来说不是必需的,并且其表达本身不足以抑制分化表型。
It is widely accepted that the cellular oncogene c-myc plays an important role in the control of cell proliferation and that its expression diminishes in differentiated cells. We examined whether there is a correlation between c-myc expression and cell proliferation or differentiation by using a subclone of a rat skeletal muscle cell line L6E9. Myoblasts irreversibly withdraw from the cell cycle, fuse to form multinucleated myotubes, and express muscle-specific genes (terminal differentiation). Muscle-specific genes can also be expressed in the absence of fusion (biochemical differentiation). Such mononucleated but biochemically differentiated cells can be stimulated to reenter the cell cycle. c-myc was induced by insulin, insulin-like growth factor, or serum factors in G0-arrested cells, whereas induction by protein synthesis inhibitors or superinduction by protein synthesis inhibitors in combination with serum factors occurred in all physiological states tested. We found that c-myc expression was reduced in biochemically and terminally differentiated cells as well as in quiescent undifferentiated cells but that it remained inducible by growth factors in all three physiological states. Results of nuclear runoff transcription assays suggested that the induction of c-myc mRNA by growth factors and its deinduction in these physiological states were regulated mainly at the transcriptional level. In contrast, induction and superinduction of c-myc mRNA by protein synthesis inhibitors alone and in combination with growth factors, respectively, were regulated posttranscriptionally mainly by stabilization of c-myc mRNA. Moreover, c-myc and muscle-specific genes could be simultaneously transcribed in both biochemically and terminally differentiated cells. These results indicate that irreversible repression of c-myc is not required for terminal myogenic differentiation and that its expression is insufficient by itself to suppress the differentiated phenotype.
生长调节素和胰岛素对体外成肌细胞分化的影响。
DOI: 10.1016/0012-1606(81)90312-2
发表时间: 1981
影响因子: 2.7
作者:
Ewton,DZ;Florini,JR
通讯作者: Florini,JR
肌肉分化的调节:α-肌动蛋白信使核糖核酸序列的克隆。
DOI: 10.1021/bi00566a034
发表时间: 1980
期刊: Biochemistry
影响因子: 2.9
作者:
Schwartz,RJ;Haron,JA;Rothblum,KN;Dugaiczyk,A
通讯作者: Dugaiczyk,A