Cells in G2/M phase increased in human nasopharyngeal carcinoma cell line by EBV-LMP1 through activation of NF-kappaB and AP-1.
Although previous studies showed that the principal oncoprotein encoded by Epstein-Barr virus, latent membrane protein 1(LMP1), could induce the nasopharyngeal carcinoma cells in G2/M phase increased, little is known about the target molecules and mechanisms. The present study demonstrated that LMP1 could induce the accumulation of p53 protein and upregulate its transactivity in a dose dependent manner, which resulted in the decrease of the kinase activity of cdc2/cyclin B complex and inducing arrest at G2/M phase through the activation of NF-kappaB and AP-1 signaling pathways, and the effect of NF-kappaB was more obvious than that of AP-1. This study provided some significant evidence for further elucidating the molecular mechanisms that LMP1 had effects on the surveillance mechanism of cell cycle and promoting the survival of transformed cells and tumorigenesis.
Deng
Lin
L
Cancer Research Institute, Xiangya School of Medicine, Central South University, Xiangya Road 88, Changsha, Hunan 410078, China.
Yang
Jing
J
Zhao
Xiao Rong
XR
Deng
Xi Yun
XY
Zeng
Liang
L
Gu
Huan Hua
HH
Tang
Min
M
Cao
Ya
Y
D015153:Blotting, Western; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D016195:G2 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000378:metabolism
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D014763:Viral Matrix Proteins; D008156:Luciferases; D016203:CDC2 Protein Kinase; D004318:Doxycycline