The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy
The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy
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DOI：
10.1038/sj.onc.1210946
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发表时间：
2008-05-01
期刊：
影响因子：
8
通讯作者：
Sugden, B.
中科院分区：
文献类型：
--
作者：
Lee, D. Y.;Sugden, B.
爱泼斯坦-巴尔病毒（EBV）是一种疱疹病毒，与几种人类癌症有关。eb病毒感染B细胞诱导和维持增殖，需要致癌基因潜伏膜蛋白1 （latent membrane protein 1, LMP1）。LMP1以不依赖于配体的方式发出信号，并且在单个克隆的细胞中以不同的水平表达。正是这种不寻常的分布使得LMP1能够刺激多种不同的通路。平均水平的LMP1诱导增殖，而高水平的LMP1诱导细胞停滞和抑制蛋白质合成。这些抑制途径是由LMP1的六个跨膜结构域诱导的。我们发现了由LMP1的跨膜结构域3-6编码的新功能；它们以剂量依赖的方式诱导自噬，从而改变宿主的生理机能。低水平表达LMP1的细胞表现为早期自噬，自噬体；那些表达高水平的癌基因显示晚期自噬，自溶酶体。抑制ebv阳性细胞的自噬导致LMP1的积累和形成菌落的能力下降。这些结果表明LMP1诱导自噬参与了自身和宿主细胞的调控。
Epstein-Barr virus (EBV) is a herpes virus that is associated with several human cancers. Infection of B cells by EBV leads to their induction and maintenance of proliferation and requires the oncogene, latent membrane protein 1 (LMP1). LMP1 signals in a ligand-independent manner and is expressed at widely different levels in cells of a single clone. It is this unusual distribution that allows LMP1 to stimulate multiple, distinct pathways. Average levels of LMP1 induce proliferation while high levels induce cytostasis and inhibition of protein synthesis. These inhibitory pathways are induced by the six transmembrane domains of LMP1. We uncovered a novel function encoded by transmembrane domains 3-6 of LMP1; they induce autophagy in a dose-dependent manner and thus, modify the physiology of their host. Cells that express low levels of LMP1 display early stages of autophagy, autophagosomes; those that express high levels of this oncogene display late stages of autophagy, autolysosomes. Inhibition of autophagy in EBV-positive cells leads to an accumulation of LMP1 and a decreased ability to form colonies. These results indicate that LMP1's induction of autophagy contributes to its own regulation and that of its host cell.