EB病毒潜伏膜蛋白1通过TRAF/TRADD激活JNK信号途径  

EB Virus-encoded Latent Membrane Protein 1 Activates The JNK Signalling Pathway via a Mechanism Involving TRADD and TRAF in Nasopharyngeal Carcinoma Cell

作　　者：胡智[1] 曾亮[1] 陶永光[1] 唐发清[1] 王海[1] 罗非君[1] 易薇[1] 曹亚[1] 

机构地区：[1]中南大学湘雅医学院肿瘤研究所,长沙410078

出　　处：《生物化学与生物物理进展》2002年第4期562-566,共5页Progress In Biochemistry and Biophysics

基　　金：国家重点基础研究发展规划"恶性肿瘤发生发展的基础研究"项目 (973 ) (G19980 5 12 0 1);国家自然科学基金项目 (3 0 0 0 0 0 87)~~

摘　　要：为了探讨在鼻咽癌细胞中EB病毒编码的潜伏膜蛋白 1(LMP1)激活c Jun氨基端激酶 (JNK)信号途径的分子机制 ,利用可调控表达LMP1的鼻咽癌细胞系L7,蛋白质印迹检测 ,发现LMP1能够促进JNK的活化 ;利用稳定表达LMP1的鼻咽癌细胞系HNE2 LMP1及其三种突变体HNE2 LMP1ΔCTAR 1、HNE2 LMP1ΔCTAR2、HNE2 LMP1ΔCTAR 1,2及LMP1阴性的HNE2 为材料 ,采用蛋白质印迹和报告基因法分析JNK和活化蛋白 1(AP1)活化情况 ,结果显示HNE2 LMP1和HNE2 LMP1ΔCTAR1中磷酸化JNK蛋白表达量和AP1活性都无显著差异 ,而与HNE2 LMP1ΔCTAR2、HNE2 LMP1ΔCTAR1,2、阴性对照HNE2及空白载体转染细胞的JNK蛋白表达和AP1活性具有显著差异 ;进一步比较转染TRAF、TRADD显性负性突变体鼻咽癌细胞系HNE2 LMP1中磷酸化的JNK量和AP1活性 ,结果显示 :TRAF DN和TRADD DN的导入使活化的JNK蛋白和AP 1活性显著降低 ,二者间无显著差异 ,提示TRAF和TRADD可能参与了LMP1对JNK和AP 1的活化 .以上结果提示在鼻咽癌细胞系中LMP1功能结构域CTAR2通过结合TRAF/TRADD激活JNK从而活化重要的转录因子AP1.In order to illustrate the mechanism of AP1 signalling pathway mediated by latent membrane protein 1 (LMP1) encoded by EB virus, the expression of phospho JNK in Tet on LMP1 HNE 2 cell line (L7) was determined at different time by Western blotting, JNK activation increased with the induction of LMP1 in a time dependant manner was abserved. The expression of phospho JNK and AP1 activity were analyzed by Western blotting and reporter gene in nasopharyngeal carcinoma cell lines which stably expressing LMP1 and the three kinds of its mutants containing different mutation in carboxyterminal activating region. The result showed that no difference existed between HNE 2 LMP1 and HNE 2 LMP1ΔCTAR1, but significant difference between HNE 2 LMP1ΔCTAR2 and HNE 2 LMP1, HNE 2 LMP1ΔCTAR1,2. The phospho JNK expression and AP1 activity of HNE 2 LMP1 cell lines were individually transfected by dominant negative TRAF(TRAF DN) and dominant negative TRADD(TRADD DN). The results showed that the transfection of TRAF DN or TRADD DN made JNK expression and AP1 activity decreased significantly. The results suggested that the functional domain CTAR2 of LMP1 encoded by EB virus can mediate JNK signalling pathway through cooperation with TRAF/TRADD complex.

关 键 词：EB病毒 潜伏膜蛋白1 TRAF/TRADD 激活 JNK信号途径 鼻咽癌 

分 类 号：R739.63[医药卫生—肿瘤]