The Epstein-Barr Virus EBNA-LP Protein Preferentially Coactivates EBNA2-Mediated Stimulation of Latent Membrane Proteins Expressed from the Viral Divergent Promoter
The Epstein-Barr Virus EBNA-LP Protein Preferentially Coactivates EBNA2-Mediated Stimulation of Latent Membrane Proteins Expressed from the Viral Divergent Promoter
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Epstein-Barr 病毒 EBNA-LP 蛋白优先共激活 EBNA2 介导的病毒趋异启动子表达的潜伏膜蛋白的刺激
DOI：
10.1128/jvi.79.7.4492-4505.2005
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发表时间：
2005
影响因子：
5.4
通讯作者：
P. Ling
中科院分区：
文献类型：
--
作者：
Rongsheng Peng;Stephanie C Moses;Jie Tan;E. Kremmer;P. Ling
摘要 Epstein-Barr 病毒 (EBV) EBNA-LP 蛋白对 B 细胞永生化的机制贡献仍然是一个谜。然而，之前的研究表明，EBNA-LP 可能通过增强 EBNA2 介导的 LMP-1 基因转录激活来促进永生化。为了进一步了解 EBNA-LP 在 EBV 介导的 B 细胞永生化中的潜在作用，我们询问它是否是 EBNA2 的全局或基因特异性共激活剂，以及共激活是否需要这些蛋白质之间的相互作用。在 I 型伯基特淋巴瘤细胞中，我们发现 EBNA-LP 强烈共激活 EBNA2 对 LMP-1 和 LMP2B RNA 的刺激，而 LMP-1 和 LMP2B RNA 由病毒趋异启动子表达。令人惊讶的是，病毒LMP2A基因以及细胞CD21和Hes-1基因被EBNA2诱导，但在EBNA-LP共表达后没有表现出进一步的诱导。我们还发现，即使条件足以观察 EBNA2 与其细胞辅助因子 CBF1 之间的特异性相互作用，EBNA-LP 在免疫共沉淀测定中也不能稳定地与 EBNA2 相互作用。在 EBV 转化的细胞系或转染的 I 型 Burkitt 细胞中未检测到 EBNA2 和 EBNA-LP 之间的共定位。最后，在哺乳动物双杂交检测中未发现 EBNA2 和 EBNA-LP 之间存在显着的相互作用。从这些数据中，我们得出结论，EBNA-LP 不是 EBNA2 靶标的全局共激活剂，但它优先共激活病毒趋异启动子的 EBNA2 刺激。虽然这可能需要这些蛋白质之间仅发生在不同启动子背景下的特定瞬时相互作用，但我们的数据强烈表明 EBNA-LP 也通过不需要这些蛋白质之间直接或间接形成复合物的机制与 EBNA2 合作。
ABSTRACT The mechanistic contribution of the Epstein-Barr virus (EBV) EBNA-LP protein to B-cell immortalization remains an enigma. However, previous studies have indicated that EBNA-LP may contribute to immortalization by enhancing EBNA2-mediated transcriptional activation of the LMP-1 gene. To gain further insight into the potential role EBNA-LP has in EBV-mediated B-cell immortalization, we asked whether it is a global or gene-specific coactivator of EBNA2 and whether coactivation requires interaction between these proteins. In type I Burkitt's lymphoma cells, we found that EBNA-LP strongly coactivated EBNA2 stimulation of LMP-1 and LMP2B RNAs, which are expressed from the viral divergent promoter. Surprisingly, the viral LMP2A gene and cellular CD21 and Hes-1 genes were induced by EBNA2 but showed no further induction after EBNA-LP coexpression. We also found that EBNA-LP did not stably interact with EBNA2 in coimmunoprecipitation assays, even though the conditions were adequate to observe specific interactions between EBNA2 and its cellular cofactor, CBF1. Colocalization between EBNA2 and EBNA-LP was not detectable in EBV-transformed cell lines or transfected type I Burkitt's cells. Finally, no significant interactions between EBNA2 and EBNA-LP were found with mammalian two-hybrid assays. From this data, we conclude that EBNA-LP is not a global coactivator of EBNA2 targets, but it preferentially coactivates EBNA2 stimulation of the viral divergent promoter. While this may require specific transient interactions between these proteins that only occur in the context of the divergent promoter, our data strongly suggest that EBNA-LP also cooperates with EBNA2 through mechanisms that do not require direct or indirect complex formation between these proteins.
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影响因子：
3.8
作者：
SZEKELY, L;JIANG, WQ;RINGERTZ, N
通讯作者：
RINGERTZ, N
编码 Epstein-Barr 病毒核蛋白的 mRNA 的核苷酸序列：可能的转录起始位点。
DOI：
10.1073/pnas.83.14.5096
发表时间：
1986
影响因子：
11.1
作者：
Sample,J;Hummel,M;Braun,D;Birkenbach,M;Kieff,E
通讯作者：
Kieff,E
DOI：
10.1073/pnas.91.16.7568
发表时间：
1994-08-02
影响因子：
11.1
作者：
GROSSMAN, SR;JOHANNSEN, E;KIEFF, E
通讯作者：
KIEFF, E
DOI：
10.1073/pnas.92.8.3259
发表时间：
1995-04
影响因子：
11.1
作者：
Xiao Tong;Ronny Drapkin;Danny Reinberg;Elliott Kieff
通讯作者：
Xiao Tong;Ronny Drapkin;Danny Reinberg;Elliott Kieff
DOI：
10.1073/pnas.90.20.9237
发表时间：
1993-10-15
影响因子：
11.1
作者：
LING, PD;RAWLINS, DR;HAYWARD, SD
通讯作者：
HAYWARD, SD