Ozaki T, Nakamura Y, Hanaoka E, Nakagawara A, Sakiyama S
Division of Biochemistry, Chiba Cancer Center Research Institute, Chuoh-ku, Chiba 260-8717, Japan.
Jpn J Cancer Res. 2000 Oct;91(10):987-93. doi: 10.1111/j.1349-7006.2000.tb00875.x.
We have recently found that DA41 exhibits marked homology with mouse PLIC-1, PLIC-2, frog XDRP1 and yeast DSK2. XDRP1 has been shown to be associated with cyclin A, and blocks cell division of frog embryo. In the present study, we examined the biological role(s) of DA41 in mammalian cells by overexpressing it in v-Ha-ras-transformed 3Y1 cells (ras-3Y1). Transfectants which expressed a high level of DA41 mRNA exhibited a decrease in growth rate, a reduction in saturation density, and a suppression of colony formation in soft agar medium. To clarify the molecular mechanism(s) by which DA41 affects cell growth, the effect of DA41 expression on the levels of various cell cycle-regulatory proteins was examined. The forced expression of DA41 gene resulted in a remarkable reduction in CDK2 activity, while the amount of CDK2 did not change. These observations indicate that DA41 is involved in cell cycle regulation in ras-3Y1 cells.
我们最近发现,DA41与小鼠PLIC-1、PLIC-2、青蛙XDRP1和酵母DSK2具有显著的同源性。XDRP1已被证明与细胞周期蛋白A相关,并能阻断青蛙胚胎的细胞分裂。在本研究中,我们通过在v-Ha-ras转化的3Y1细胞(ras-3Y1)中过表达DA41来研究其在哺乳动物细胞中的生物学作用。表达高水平DA41 mRNA的转染子在生长速率上有所下降,饱和密度降低,并且在软琼脂培养基中的集落形成受到抑制。为了阐明DA41影响细胞生长的分子机制,我们检测了DA41表达对各种细胞周期调节蛋白水平的影响。DA41基因的强制表达导致CDK2活性显著降低,而CDK2的量没有变化。这些观察结果表明,DA41参与了ras-3Y1细胞的细胞周期调控。