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-κB and AP-1 signaling pathways, and the effect of NF-κB 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.
Latent membrane protein 1 (LMP1), an important protein encoded by Epstein Barr virus (EBV), has been implied to link with the pathogenesis of nasopharyngeal carcinoma (NPC). Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line-CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G 2 /M phase, our studies suggested that LMP1 could promote the expression of Survivin in G 0 /G 1 , S and G 2 / M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMP1. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.
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