Zhang Xiangning, Hu LiFu, Fadeel Bengt, Ernberg Ingemar T
Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Virology. 2002 Dec 20;304(2):330-41. doi: 10.1006/viro.2002.1640.
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is required for viral transformation and has been shown to protect lymphocytes from apoptosis. However, the effect of LMP1 on cells of epithelial origin remains poorly understood. Using the epithelial cell line HeLa in which the expression of LMP1 is inducibly regulated by tetracycline, we demonstrate that apoptosis triggered by ligation of the death receptor, Fas, or by the chemotherapeutic agent, etoposide, is potentiated by LMP1. Apoptosis was assessed by nuclear condensation and activation of caspase-3-like enzymes with concomitant proteolysis of the nuclear caspase substrate, poly(ADP-ribose) polymerase. However, the effect of LMP1 in HeLa cells appeared to be stimulus-dependent since apoptosis induced by tumor necrosis factor (TNF) was inhibited. Moreover, we observed an upregulation of the zinc finger protein A20 and a decrease in expression of Bcl-2 upon induction of LMP1 in HeLa cells. Taken together, these data further our understanding of the function of LMP1 in epithelial cells and suggest that LMP1, similar to its mammalian homolog CD40, can exert opposing effects on cell survival depending on the nature of the apoptosis trigger.
爱泼斯坦-巴尔病毒（EBV）编码的潜伏膜蛋白1（LMP1）是病毒转化所必需的，并且已被证明可保护淋巴细胞免于凋亡。然而，LMP1对上皮来源细胞的影响仍知之甚少。利用四环素可诱导调节LMP1表达的上皮细胞系HeLa，我们证明LMP1增强了由死亡受体Fas的连接或化疗药物依托泊苷引发的凋亡。通过核浓缩和激活类似caspase-3的酶并伴随核caspase底物聚（ADP-核糖）聚合酶的蛋白水解来评估凋亡。然而，LMP1对HeLa细胞的作用似乎是刺激依赖性的，因为肿瘤坏死因子（TNF）诱导的凋亡受到抑制。此外，我们观察到在HeLa细胞中诱导LMP1后锌指蛋白A20上调且Bcl-2表达下降。综上所述，这些数据加深了我们对LMP1在上皮细胞中功能的理解，并表明LMP1与其哺乳动物同源物CD40类似，根据凋亡触发因素的性质可对细胞存活产生相反的影响。
