Falcone G, Alemà S, Tatò F
Istituto di Biologia Cellulare, Consiglio Nazionale delle Ricerche, Università La Sapienza, Rome, Italy.
Mol Cell Biol. 1991 Jun;11(6):3331-8. doi: 10.1128/mcb.11.6.3331-3338.1991.
Quail myogenic cells infected with temperature sensitive (ts) mutants of Rous sarcoma virus (RSV) exhibit a temperature-dependent transformation and block of differentiation. When the cells are allowed to differentiate at the restrictive temperature (41 degrees C) and then shifted back to the permissive temperature (35 degrees C), a sharp reduction in the accumulation of muscle-specific mRNAs is observed, following reactivation of the transforming protein pp60v-src. A kinetic analysis of this down-regulation reveals that the reduction in the accumulation of muscle-specific transcripts occurs fairly rapidly within 6 to 20 h after the shift back, depending on the mRNA analyzed. Studies on transcription of endogenous muscle-specific genes and a transfected chloramphenicol acetyltransferase reporter gene under the control of muscle-specific promoters, at the different temperatures, suggest that the oncogene exerts its control mainly at the transcriptional level. On the contrary, transcription of the CMD1 gene, the avian homolog of the mouse muscle regulatory MyoD gene, is not significantly affected by the oncogene both in proliferating myoblasts and in myotubes shifted back to 35 degrees C. These findings are consistent with the conclusion that v-src blocks myogenesis by controlling transcription of muscle-specific genes independently of cell proliferation. Furthermore, they suggest the existence of an alternative pathway, not requiring the silencing of CMD1 transcription, through which the oncogene exerts its effect.
感染劳斯肉瘤病毒（RSV）温度敏感（ts）突变体的鹌鹑成肌细胞表现出温度依赖性转化和分化阻滞。当细胞在限制温度（41摄氏度）下分化，然后再转移回允许温度（35摄氏度）时，在转化蛋白pp60v-src重新激活后，观察到肌肉特异性mRNA的积累急剧减少。对这种下调的动力学分析表明，肌肉特异性转录本积累的减少在转移回后6至20小时内相当迅速地发生，这取决于所分析的mRNA。在不同温度下对内源性肌肉特异性基因转录以及在肌肉特异性启动子控制下的转染氯霉素乙酰转移酶报告基因的研究表明，癌基因主要在转录水平发挥其调控作用。相反，CMD1基因（小鼠肌肉调节基因MyoD的禽类同源物）的转录在增殖的成肌细胞和转移回35摄氏度的肌管中均未受到癌基因的显著影响。这些发现与v-src通过独立于细胞增殖控制肌肉特异性基因转录来阻断肌生成的结论一致。此外，它们表明存在一条不需要CMD1转录沉默的替代途径，癌基因通过该途径发挥其作用。
