Overexpression of DA41 in v-Ha-ras-3Y1 cells causes growth suppression.

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.