EB病毒LMP1羧基端胞浆区介导端粒酶活化

目的 探讨EB病毒LMP1羧基端胞浆区与端粒酶活化的关系。方法 利用四环素衍生物强力霉素(Dox)调控LMP1表达的鼻咽癌细胞p^Tet-on-LMP1 HNE2，检测Dox诱导时细胞表达的端粒酶活性；将野生型LMP1表达质粒及其羧基端胞浆区、CTAR1功能域和CTAR2功能域分别缺失的表达质粒分别转染LMP1阴性的鼻咽癌细胞HNE2，观察端粒酶活性的变化情况。结果 在Dox诱导下，细胞表达的端粒酶活性较强；若HNE2细胞转染LMP1基因后，端粒酶活性明显升高。将LMP1羧基端胞浆区完全缺失后，端粒酶活性明显下降；若分别缺失CTAR1功能域和CRAR2功能域，端粒酶活性分别下降了4．43倍和2．88倍。结论 EB病毒LMP1可活化端粒酶活性，这一功能与LMP1羧基端胞浆区，特别是其功能域CTAR1和CTAR2密切相关。

Telomerase activation is medicated by the carboxyl terminus region of Epstein-Barr virus LMP1

Objective To study the relationship between carboxyl terminus tegion of EBV LMP1 and telomerase activation.Methods A Tet-on-LMP1 nasopharyngeal carcinoma cell line,named Tet-on-LMP1 HNE2,was used to test telomerase activity when Tet-on-LMP1 HNE2 cells were treated by Doxycycline(Dox).In this study,a wild-type plasmid that contains total amino acids of LMP1 and three mutants of LMP1 that were respectively lack of the whole carboxyl terminus of LMP1,only lack of CTAR1 domain of LMP1 and only lack of CTAR2 domain of LMP1 were also respectively transfected into a NPC cell line,HNE2,that do not express LMP1 to detect telomerase activity.Results The telomerase activity was enhanced when Tet-on-LMP1 HNE2 cells were treated by Dox.Also,the telomerase activity was obviously increased when HNE2 cells were transfected by wild-type LMP1 plasmid.Furthermore,the telomerase activity induced by LMP1 was regulated down when the whole carboxy1 terminus of LMP1 was laced.In addition,the telomerase activity induced by LMP1 was respectively decreased 4 43 folds and 2 88 folds when CTAR1 domain and CTAR2 domain were respectively lacked.Conclusion EBV LMP1 is able to activate telomerase and this function is related to the carboxyl terminus region of LMP1,specially CTAR1 domain and CTAR2 domain.