Levels of p53 in Epstein-Barr virus-infected cells determine cell fate: Apoptosis, cell cycle arrest at the G1/S boundary without apoptosis, cell cycle arrest at the G2/M boundary without apoptosis, or unrestricted proliferation
Levels of p53 in Epstein-Barr virus-infected cells determine cell fate: Apoptosis, cell cycle arrest at the G1/S boundary without apoptosis, cell cycle arrest at the G2/M boundary without apoptosis, or unrestricted proliferation
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DOI：
10.1006/viro.1998.9431
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发表时间：
1998-11-25
期刊：
影响因子：
3.7
通讯作者：
Cooper, NR
中科院分区：
文献类型：
--
作者：
Chen, WP;Huang, S;Cooper, NR
在EB病毒（EBV）感染和永生性B淋巴母细胞样细胞系（LCL）的产生过程中发生的p53和p21/WAF 1水平的显著增加不会导致生长停滞或凋亡，尽管通过转染或DNA损伤增加EBV感染细胞中的野生型（wt）p53水平会诱导这些效应。我们假设p53相对于LMP 1的浓度决定了EBV感染的B细胞是否发生生长停滞和凋亡。细胞周期阻滞和细胞凋亡进行了评估，在LCL表达不同的p53水平，通过处理细胞与顺铂浓度增加，我们补充了这种方法与实验在EB病毒感染的伯基特淋巴瘤（BL）细胞转染的温度敏感（TS）突变型人p53和研究在LCL感染重组腺病毒表达野生型和TS突变型p53。p53和p21/WAFI的小幅增加导致细胞周期停滞在G2/M边界，但不凋亡;中度增加导致生长停滞在G1/S边界，也没有凋亡;和大的增加也诱导凋亡。这些结果证实了这一假设，并揭示了p53在细胞周期调控中的意想不到的复杂性，（C）1998年学术出版社。
The marked increases in p53 and p21/WAF1 levels that occur during Epstein-Barr virus (EBV) infection and the generation of immortal B lymphoblastoid cell lines (LCL) do not lead to growth arrest or apoptosis, although increasing wild-type (wt) p53 levels in EBV-infected cells by transfection or DNA damage induce these effects. We hypothesized that the concentration of p53 relative to that of LMP1 determines whether EBV-infected B cells undergo growth arrest and apoptosis. Cell cycle arrest and apoptosis were evaluated in LCL expressing varying p53 levels achieved by treating the cells with increasing concentrations of cisplatin, and we supplemented this approach with experiments in EBV-infected Burkitt's lymphoma (BL) cells transfected with a temperature-sensitive (ts) mutant human p53 and studies in LCL infected with recombinant adenoviruses expressing wt and ts mutant p53. Small increases in p53 and p21/WAFI led to cell cycle arrest at the G2/M boundary, but not to apoptosis; moderate increases resulted in growth arrest at the G1/S boundary, also without apoptosis; and large increases also induced apoptosis. These results confirm the hypothesis and reveal unanticipated complexities in cell cycle regulation by p53, (C) 1998 Academic Press.