EBV LMP1通过诱导c-myc表达活化端粒酶hTERT

Epstein-Barr Virus LMP1 Activates Human Telomerase Transcription via c-myc Expression

利用原代人胚鼻咽上皮细胞和Tet on LMP1HNE2等良好的细胞体系,采用报道基因法和Westernblot法等,分别检测Epstein Barr病毒(EBV)潜伏膜蛋白1(LMP1)诱导的c myc反式激活活性和蛋白表达水平,从LMP1诱导细胞内c myc表达的角度,探讨LMP1诱导端粒酶表达的分子机制。结果表明,LMP1促使细胞内c myc反式激活活性增强,c Myc蛋白表达量升高;导入反义LMP1表达质粒阻断LMP1表达后,c myc反式激活活性下降。将端粒酶hTERT启动子上c myc结合位点突变后,LMP1不能诱导端粒酶hTERT表达。因而认为,EB病毒LMP1通过诱导c myc表达而活化端粒酶hTERT。

Latent membrane protein 1 (LMP1), one of the oncoprotein enco ded by Epstein-Barr virus,is suffi cient for development of nasophary ngeal carcinoma in vivo and naso pharyngeal epithelial cell immortali zation in vitro.Aslo, it has bee n shown to increase the telomerase en zyme activity in primary human nas opharyngeal epithelial cells by an unknown mechanism.We report here that a study using reporter gene as say in transduced primary human na sopharyngeal epithelial cells and a Tet-on-LPM1 nasopharyngeal carci noma cell line,named Tet-on-LMP1 H NE2 shows that LMP1 induces c-myc protein expression and enhances th e transactivation of c-myc.Mutati on of the minimal hTERT promoter c ontaining c-myc-responsive E-box e lements can down-regulate the expr ession of hTERT induced by LMP1,su ggesting a role for c-myc protein in LMP1 mediated telomerase reacti vation.These findings suggest that telomerase is a target of LMP1 and telomerase activation by LMP1 is t hrough c-myc expression.