RNA Silencing Suppressor p19 Regulates the Expressions of Cell Cycle Related Genes
RNA Silencing Suppressor p19 Regulates the Expressions of Cell Cycle Related Genes
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DOI：
10.3724/sp.j.1206.2009.00009
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发表时间：
2009-05
影响因子：
0.3
通讯作者：
Li Liu;Jian Li;Yu-ping Xu;W. Qiao;Qi-min Chen;Y. Geng
中科院分区：
文献类型：
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作者：
Li Liu;Jian Li;Yu-ping Xu;W. Qiao;Qi-min Chen;Y. Geng
除了作为致病决定基因的功能外，Tombus病毒P19还通过隔离细胞内的小RNA，如小干扰RNAs(SiRNAs)和microRNAs(MiRNAs)，发挥抑制RNA干扰(RNAi)的作用。然而，P19对哺乳动物细胞的作用以前还没有被评估过。建立了稳定表达p19(HEK293-p19)的人胚胎肾293细胞系。流式细胞仪分析显示，P19过表达导致G2/M期细胞明显积聚。细胞增殖实验显示HEK293-p19细胞的DNA复制和细胞生长受到抑制。此外，p19还改变了HEK293细胞中一些细胞周期调节因子的表达谱，如上调细胞周期蛋白A1、CDK2、CDK4、CDK6、p18、细胞周期蛋白D2、pl9INK4d和E2F1，下调细胞周期蛋白p15、细胞周期蛋白A2、细胞周期蛋白BI和细胞周期蛋白E1.因此，数据有力地表明，p19可能影响多个G2/M调节因子，导致G2/M停滞。
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.