Abstract
Besides its function as a pathogenicity determinant, the Tombusvirus P19 also serves as a suppressor of RNA interference (RNAi) by sequestering intracellular small RNAs such as the small interfering RNAs (siRNAs) and microRNAs (miRNAs). However, the effect of P19 on mammalian cells has not been evaluated before. A human embryonic kidney 293 cell line that stably expressed p19 (HEK293-p19) was generated. Flow cytometric analysis revealed that over-expression of P19 caused a significant accumulation of G2/M phase cells. Cell proliferation assays demonstrated a reduced DNA replication and cell growth in HEK293-p19 cells. Moreover, p19 altered the expression profiles of a number of cell cycle regulators in HEK293 cells, such as upregulation of cyclin Al, CDK2, CDK4, CDK6, p18, cyclin D2, pl9INK4d and E2F1, and downregulation of p15, cyclin A2, cyclin BI and cyclin El. Thus, the data strongly indicate that p19 might influence multiple G2/M regulators to cause G2/M arrest.
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