Nuclear translocation of EGF receptor regulated by Epstein-Barr virus encoded latent membrane protein 1  

作　　者：TAO Yongguang1, SONG Xin1, TAN Yunnian1, LIN Xiaofeng2, ZHAO Yan1, ZENG Liang1, TANG Min1, LI Wei1, WU Qiao2 & CAO Ya1 1. Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, China 2. Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, China 

出　　处：《Science China(Life Sciences)》2004年第3期258-267,共10页中国科学（生命科学英文版）

基　　金：This work was supported by the National Natural Science Foundation for Distinguished Young Scholar of China(No.3952502);State Key Basic Research Program,Fundamental Investigation on Human Carcinogenesis of China(No.G1998051201);National Natural Science Foundation of China(Grant No.30300407).

摘　　要：Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV encoded proteins, and also it has always been the core of the oncogenic mechanism of EBV. Traditional receptor theory demonstrates that cell surface receptors exert biological functions on the membrane, which neither enter into the nucleus nor directly affect the transcription of the target genes. But, advanced studies on nuclear transloca-tion of the epidermal growth factor receptor (EGFR) family have greatly developed our knowl-edge of the biological function of cell surface receptors. In this study, we used Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1 integrated NPC cell line and the ex-pression of LMP1 in which could be regulated by Tet system. We found that LMP1 could regulate the nuclear translocation of EGFR in a dose-dependent manner from both quantitative and qualitative levels through the Western blot analysis and the immunofluorescent analysis with a laser scanning confocal microscope. We further demonstrated that the nuclear localization se-quence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation, and the nuclear accumulation of EGFR regulated by LMP1 was in a ligand-independent manner. These findings provide a novel view that the regulation of LMP1 on the nuclear translocation of EGFR is critical for the process of nasopharyngeal carcinoma.Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV encoded proteins, and also it has always been the core of the oncogenic mechanism of EBV. Traditional receptor theory demonstrates that cell surface receptors exert biological functions on the membrane, which neither enter into the nucleus nor directly affect the transcription of the target genes. But, advanced studies on nuclear transloca-tion of the epidermal growth factor receptor (EGFR) family have greatly developed our knowl-edge of the biological function of cell surface receptors. In this study, we used Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1 integrated NPC cell line and the ex-pression of LMP1 in which could be regulated by Tet system. We found that LMP1 could regulate the nuclear translocation of EGFR in a dose-dependent manner from both quantitative and qualitative levels through the Western blot analysis and the immunofluorescent analysis with a laser scanning confocal microscope. We further demonstrated that the nuclear localization se-quence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation, and the nuclear accumulation of EGFR regulated by LMP1 was in a ligand-independent manner. These findings provide a novel view that the regulation of LMP1 on the nuclear translocation of EGFR is critical for the process of nasopharyngeal carcinoma.

关 键 词：Epstein-Bar virus  LATENT membrane protein 1  EPIDERMAL growth factor receptor  nuclear translocation. 

分 类 号：Q51[生物学—生物化学]