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作 者:罗非君[1] 胡智[1] 邓锡云[1] 翁新宪[1] 易微[1] 曹亚[1]
出 处:《中国生物化学与分子生物学报》2001年第3期381-385,共5页Chinese Journal of Biochemistry and Molecular Biology
基 金:国家重点基础研究发展规划 ( 973 )"恶性肿瘤发生发展的基础研究"项目 (No.G19980 5 12 0 1);国家自然科学基金 (No .3 0 0 0 0 0 87)
摘 要:EB病毒潜伏膜蛋白 1 (latentmembraneprotein 1 ,LMP 1 )活化激活蛋白 1 (activatorprotein 1 ,AP 1 )信号传导途径与其致瘤作用密切相关 .为了探讨LMP 1活化AP 1信号传导的分子机制 ,在可诱导调控LMP 1表达的鼻咽癌细胞系L7中 ,首先通过荧光酶双报道系统确定了LMP 1表达能激活AP 1 ;在此基础上 ,用c JunPathDetect系统确定LMP 1表达活化AP 1是通过c Jun的磷酸化 (活化 )介导 .虽然LMP 1不能上调c Jun上游主要调节激酶c JunN端激酶 (c JunN terminalkinase ,JNK)的蛋白表达 ,但能显著促进JNK的磷酸化 (活化 ) ;在L7细胞中导入JNK相互作用蛋白 (JNK interactingprotein ,JIP)基因 ,抑制JNK的核移位能显著抑制LMP 1诱导的AP 1活化 ,同时对NFкВ活化也有部分抑制作用 .结果表明 ,EB病毒LMP 1在鼻咽癌细胞中通过JNK介导APIn order to investigate the signaling transduction mechanisms of Epstein\|Barr virus latent membrane 1(LMP\|1)activating nuclear transcription factor activator(AP\|1),in Dox\|induced expression of LMP\|1 nasopharyngeal carcinoma cell line L7,the effects of LMP\|1 on the activities of AP\|1 and NFκB were analyzed by dual\|reporter system;the phosphorylation of c\|Jun N\|terminal kinase (JNK) was analyzed by Western blotting;furthermore,the effects of JNK\|interacting protein(JIP)on the activities of AP\|1 and NFκB were analyzed by dual\|reporter system.The result showed that with the increase of expression of LMP\|1,activities of AP\|1 and NFκB increased approximately 4—5 folds in L7 NPC cell line;and the signal transduction of AP\|1 was mediated by activation of c\|Jun.Although the expression of JNK remained unchanged,the phosphorylation of JNK changed with expression of LMP\|1.Moreover,JIP could partly inhibit activation of AP\|1 and retard nuclear translocation of JNK in nasopharyngeal carcinoma cell line.The results suggest that LMP\|1 can activate AP\|1 through phosphorylation of JNK in NPC cell line.
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