Epstein-Barr病毒潜伏蛋白1通过核转录因子κB诱导鼻咽上皮细胞表达端粒酶活性
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国家重点基础研究发展规划(973)“鼻咽癌发生发展的基础研究”(G1998051201)和国家自然科学基金杰出青年基金(39525022)资助.


Epstein-Barr Virus Latent Membrane Protein 1 Induces Telomerase Activity of Nasopharyngeal Epithelial Cells Through NFκB
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This work was supported by grants from The Special Funds for Major State Basic Research of China (G1998051201) and The Youth Fund of National Science Foundation of China (395250022).

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    摘要:

    利用已建立的原代人胚鼻咽上皮细胞和Tet-on-LMP1系统等良好的实验模型,采用荧光酶报道基因分析法和端粒酶TRAP-ELISA技术,分别检测EB病毒潜伏蛋白1(LMP1)诱导的核转录因子κB(NFκB)活性和端粒酶活性,从LMP1介导NFκB信号传导途径角度,探讨LMP1诱导端粒酶表达的分子机制.结果表明,LMP1可诱导鼻咽上皮细胞表达端粒酶活性,将LMP1羧基端胞浆区突变后,可同时下调NFκB活性和端粒酶活性.在Doxycycline诱导LMP1表达状态下,NFκB反式激活活性增强,同时端粒酶活性升高;进一步应用硫代磷酸化修饰的反义NFκB p65寡脱氧核苷酸和IκBα的显性负性突变体分别阻断NFκB活性,可降低由LMP1诱导的端粒酶活性.因此,NFκB作为LMP1信号传导途径上的枢纽,可能介导了LMP1对端粒酶的表达调控.

    Abstract:

    To confirm whether Epstein-Barr virus latent membrane protein 1 (LMP1) induced telomerase activity of nasopharyngeal epithelial cells through nuclear factor-kappa B(NFκB), NFκB activity analysis was performed with pNFκB-luc reporter plasmid and telomerase activity was tested by PCR-ELISA in primary nasopharyngeal epithelial cells and Tet-on-LMP1 HNE2 cells and other cellular model. The results showed that LMP1 could induce telomerase activity and the C terminus of LMP1 could promote both of NFκB transactivity and telomerase activity. In addition, phosphorothioate olrgonucleotides of antisense NFκB p65 and dominant negative mutant of IκBα could inhibit telomerase activity that was induced by LMP1. It was implicated that LMP1 could regulate telomerase activity via NFκB in nasopharyngeal epithelial cells.

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杨静,邓锡云,唐敏,吴尚辉,顾焕华,易薇,曹亚. Epstein-Barr病毒潜伏蛋白1通过核转录因子κB诱导鼻咽上皮细胞表达端粒酶活性[J].生物化学与生物物理进展,2002,29(4):556-561

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  • 收稿日期:2001-12-11
  • 最后修改日期:2002-02-09
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