Nuclear accumulation of epidermal growth factor receptor and acceleration of G1/S stage by Epstein-Barr-encoded oncoprotein latent membrane protein 1.
Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is considered to be the major oncogenic protein of EBV-encoded proteins and has always been the core of the oncogenic mechanism of EBV. Advanced studies on nuclear translocation of the epidermal growth factor receptor (EGFR) family have greatly improved our knowledge of the biological function of cell surface receptors. In this study, we used the Tet-on LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1-integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 which could be regulated by the Tet system. We found that LMP1 could regulate the nuclear accumulation of EGFR in a dose-dependent manner quantitatively and qualitatively. We also demonstrated that the nuclear localization sequence of EGFR played some roles in the location of the protein within the nucleus under LMP1 regulation and EGFR in the nucleus could bind to the promoters of cyclinD1 and cyclinE, respectively. We further demonstrated that EGFR is involved in the acceleration of the G1/S phase transition by LMP1 through binding to cyclinD1 and cyclinE directly. These findings provided a novel view that the acceleration of LMP1 on the G1/S transition via the nuclear accumulation of EGFR was critical in the process of nasopharyngeal carcinoma.
Tao
Yongguang
Y
Cancer Research Institute, Xiangya School of Medicine, Central South of University, 110, Xiangya Road, Changsha, Hunan 410078, China.
Song
Xing
X
Deng
Xiyun
X
Xie
Daxin
D
Lee
Leo M
LM
Liu
Yiping
Y
Li
Wei
W
Li
Lili
L
Deng
Lin
L
Wu
Qiao
Q
Gong
Jianping
J
Cao
Ya
Y
D001483:Base Sequence; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D004273:DNA, Neoplasm / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D066246:ErbB Receptors / Q000378:metabolism*; D016193:G1 Phase; D004854:Herpesvirus 4, Human / Q000378:metabolism* / Q000472:pathogenicity*; D006801:Humans; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000821:virology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016196:S Phase; D014763:Viral Matrix Proteins / Q000378:metabolism*
D019927:Cyclin E; D004273:DNA, Neoplasm; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D019938:Cyclin D1; D066246:ErbB Receptors