The Latent Membrane Protein 1 (LMP1) Oncogene of Epstein-Barr Virus Can Simultaneously Induce and Inhibit Apoptosis in B Cells
The Latent Membrane Protein 1 (LMP1) Oncogene of Epstein-Barr Virus Can Simultaneously Induce and Inhibit Apoptosis in B Cells
复制标题
DOI：
10.1128/jvi.06966-11
复制
发表时间：
2012-04-01
影响因子：
5.4
通讯作者：
Sugden, Bill
中科院分区：
文献类型：
--
作者：
Pratt, Zachary L.;Zhang, Jingzhu;Sugden, Bill
Epstein-Barr 病毒 (EBV) 的潜伏膜蛋白 1 (LMP1) 通过其两个功能部分调节自身表达和人类基因的表达； LMP1 的跨膜结构域需要通过 B 细胞中的未折叠蛋白反应 (UPR) 和自噬来调节其表达，LMP1 的羧基末端结构域可激活影响细胞增殖和存活的细胞信号传导通路。 LMP1 对 UPR 和自噬的复杂调节的一个明显异常是，任一途径的诱导都会导致细胞死亡，但 EBV 感染的 B 细胞和仅表达 LMP1 的 B 细胞都不会死亡。因此，我们试图了解表达 LMP1 的 B 细胞如何存活。 LMP1的跨膜结构域激活B细胞的凋亡，这种凋亡需要UPR，而LMP1的羧基末端结构域则阻断这种凋亡。 Bcl2a1 mRNA 的表达（编码 BCL2 的抗凋亡同源物）与 EBV 阳性 B 细胞株中 LMP1 的表达直接相关，并且其表达抑制 LMP1 跨膜结构域诱导的细胞凋亡。这些发现说明了 LMP1 的羧基末端结构域如何在这种病毒癌基因的复杂调节产生有害影响的情况下支持 B 细胞的存活。
The latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) regulates its own expression and the expression of human genes via its two functional moieties; the transmembrane domains of LMP1 are required to regulate its expression via the unfolded protein response (UPR) and autophagy in B cells, and the carboxy-terminal domain of LMP1 activates cellular signaling pathways that affect cellular proliferation and survival. An apparent anomaly in the complex regulation of the UPR and autophagy by LMP1 is that the induction of either pathway can lead to cellular death, yet neither EBV-infected B cells nor B cells expressing only LMP1 die. Thus, we sought to understand how B cells that express LMP1 survive. The transmembrane domains of LMP1 activated apoptosis in B cells, the apoptosis required the UPR, and the carboxy-terminal domain of LMP1 blocked this apoptosis. The expression of the mRNA of Bcl2a1, encoding an antiapoptotic homolog of BCL2, correlated directly with the expression of LMP1 in EBV-positive B-cell strains, and its expression inhibited the apoptosis induced by the transmembrane domains of LMP1. These findings illustrate how the carboxy-terminal domain of LMP1 supports survival of B cells in the presence of the deleterious effects of the complex regulation of this viral oncogene.