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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Epstein-Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintenance of lymphoblastoid cells
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Epstein-Barr virus nuclear protein EBNA3C is required for cell cycle progression and growth maintenance of lymphoblastoid cells

机译：爱泼斯坦-巴尔病毒核蛋白EBNA3C是淋巴母细胞的细胞周期进程和生长维持所必需的

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摘要

Epstein-Barr virus (EBV) infection converts primary human B cells into continuously proliferating lymphoblastoid cell lines (LCLs). To examine the role of EBV nuclear antigen (EBNA) 3C in the proliferation of LCLs, we established LCLs infected with an EBV recombinant that expresses EBNA3C with a C-terminal fusion to a 4-hydroxytamoxifen (4HT)-dependent mutant estrogen receptor, E3C-HT. In the presence of 4HT, LCLs expressed the E3C-HT protein and grew like WT LCLs. When E3C-HT EBV-infected LCLs were transferred to medium without 4HT, E3C-HT protein slowly disappeared, and the LCLs gradually ceased growing. WT EBNA3C expression from an oriP plasmid transfected into E3C-HT LCLs protected the LCLs from growth arrest in medium without 4HT, whereas expression of EBNA3A or EBNA3B did not. The expression of other EBNA proteins and of LMP1, CD21, CD23, and c-myc was unaffected by EBNA3C inactivation. However, EBNA3C inactivation resulted in the accumulation of p16(INK4A), a decrease in the hyper-phosphorylated form of the retinoblastoma protein, and a decrease in the proportion of cells in S or G(2)/M phase. These results indicate that EBNA3C has an essential role in cell cycle progression and the growth maintenance of LCLs.
机译：爱泼斯坦巴尔病毒（EBV）感染将人类原代B细胞转化为持续增殖的淋巴母细胞样细胞系（LCL）。为了检查EBV核抗原（EBNA）3C在LCL增殖中的作用，我们建立了感染EBV重组体的LCL，该重组体表达EBNA3C，其C端融合了4-羟基他莫昔芬（4HT）依赖性突变雌激素受体E3C -H T。在存在4HT的情况下，LCL表达E3C-HT蛋白并像WT LCL一样生长。当将感染E3C-HT EBV的LCL转移到不含4HT的培养基中时，E3C-HT蛋白缓慢消失，并且LCL逐渐停止生长。转染入E3C-HT LCL的oriP质粒的WT EBNA3C表达可保护LCL免受在没有4HT的培养基中的生长停滞，而EBNA3A或EBNA3B的表达则不能。 EBNA3C失活不会影响其他EBNA蛋白以及LMP1，CD21，CD23和c-myc的表达。但是，EBNA3C失活导致p16（INK4A）的积累，视网膜母细胞瘤蛋白的超磷酸化形式的减少，以及S或G（2）/ M期中细胞比例的减少。这些结果表明，EBNA3C在细胞周期进程和LCL的生长维持中具有重要作用。

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