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首页> 外文期刊>Journal of Molecular Biology >Epstein-Barr virus nuclear antigen 2 retards cell growth, induces p21(WAF1) expression, and modulates p53 activity post-translationally
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Epstein-Barr virus nuclear antigen 2 retards cell growth, induces p21(WAF1) expression, and modulates p53 activity post-translationally

机译：爱泼斯坦-巴尔病毒核抗原2抑制细胞生长，诱导p21（WAF1）表达，并在翻译后调节p53活性

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The Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) has been shown to be required for promotion of cell-cycle progression in EBV-immortalized B-lymphocytes. However, other studies have indicated that EBNA2 alone, in the absence of other EBV genes, may retard cell growth. To resolve this discrepancy, we investigated the effect of EBNA2 on the growth of various cells, including EBV target nasopharyngeal carcinoma cells, NPC-TWO1 and NPC-TW04. We found that EBNA2 could retard cell, growth, in stable Vero, HEp-2, and U20S cell clones expressing EBNA2 and in Vero, 293, NPC-TWO1, and NPC-TW04 cells transiently transfected with EBNA2. While investigating the mechanism underlying the growth-retarding function of EBNA2, we found that EBNA2 induced p21(WAF1) expression in these cells, This induction of p21(WAF1) expression was mediated through p53. EBNA2 was found to stimulate p53 to bind to the p53-response element within the p21(WAF1) promoter, possibly by promoting p53 phosphorylation. This enhancement of p53 sequence-specific DNA-binding activity may be the mechanism through which EBNA2 activates the expression of p53-regulated genes, including p21(WAF1) and mdm-2. Together, these studies reveal a possible intrinsic function of EBNA2 in cell-growth regulation and elucidate a novel mechanism by which EBNA2 modulates transcription. (C) 2000 Academic Press. [References: 67]
机译：爱泼斯坦-巴尔病毒（EBV）核抗原2（EBNA2）已被证明是促进EBV永生化B淋巴细胞中细胞周期进程的必需物质。但是，其他研究表明，在没有其他EBV基因的情况下，单独的EBNA2可能会延迟细胞的生长。为了解决这一差异，我们研究了EBNA2对各种细胞生长的影响，包括EBV靶鼻咽癌细胞，NPC-TWO1和NPC-TW04。我们发现EBNA2可以在表达EBNA2的稳定Vero，HEp-2和U20S细胞克隆中以及在用EBNA2瞬时转染的Vero，293，NPC-TWO1和NPC-TW04细胞中抑制细胞生长。在研究EBNA2延缓生长的潜在机制时，我们发现EBNA2诱导了这些细胞中p21（WAF1）的表达，p21（WAF1）表达的这种诱导是通过p53介导的。发现EBNA2可能通过促进p53磷酸化来刺激p53与p21（WAF1）启动子中的p53反应元件结合。 p53序列特异性DNA结合活性的这种增强可能是EBNA2激活p53调控基因（包括p21（WAF1）和mdm-2）表达的机制。总之，这些研究揭示了EBNA2在细胞生长调节中的潜在内在功能，并阐明了EBNA2调节转录的新机制。 （C）2000学术出版社。 [参考：67]

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