Kranenburg O, Keblusek P, Van der Eb A J, Zantema A
Department of Molecular Carcinogenesis, Sylvius Laboratory, Leiden University, The Netherlands.
J Virol. 1996 Nov;70(11):7804-10. doi: 10.1128/JVI.70.11.7804-7810.1996.
Expression of the gene encoding the cell cycle regulator cyclin D1 is strongly repressed in adenovirus type 5 E1 (Ad5E1)-transformed cells. Since cyclin D1 is a regulator of cell proliferation, modulation of its abundance may affect cell cycle control. Therefore, we studied the importance of cyclin D1 repression for cell transformation by Ad5E1. We found that forced expression of cyclin D1 does not affect the transforming potential of Ad5E1. Similarly, cyclin D1 overexpression did not affect the efficiency of colony formation, the proliferation rate, or the cell cycle distribution of Ad5E1-transformed cell lines, whereas the colony formation of untransformed cell lines was strongly inhibited. Thus, repression of cyclin D1 expression is not required for initiation or maintenance of cell transformation by Ad5E1. In addition, we show that the growth-suppressive effect of cyclin D1 correlates with cyclin D1 binding to cdk4 rather than to proliferating cell nuclear antigen PCNA.
编码细胞周期调节因子细胞周期蛋白D1的基因表达在5型腺病毒E1(Ad5E1)转化的细胞中受到强烈抑制。由于细胞周期蛋白D1是细胞增殖的调节因子,其丰度的调节可能会影响细胞周期控制。因此,我们研究了细胞周期蛋白D1抑制对Ad5E1细胞转化的重要性。我们发现,细胞周期蛋白D1的强制表达不会影响Ad5E1的转化潜能。同样,细胞周期蛋白D1的过表达不会影响Ad5E1转化细胞系的集落形成效率、增殖速率或细胞周期分布,而未转化细胞系的集落形成则受到强烈抑制。因此,Ad5E1引发或维持细胞转化不需要抑制细胞周期蛋白D1的表达。此外,我们表明细胞周期蛋白D1的生长抑制作用与细胞周期蛋白D1与细胞周期蛋白依赖性激酶4(cdk4)结合而非与增殖细胞核抗原PCNA结合相关。