ARTICLE

Cell Research, 15(10):777-784, October 2005

Regulation of Survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines

Mi Dan AI¹, Li Li LI¹, Xiao Rong ZHAO¹, Yong WU¹, Jian Ping GONG², Ya CAO^1,*

¹Cancer Research Institute, Xiangya School of Medicine, Central South University, 110 Xiangya Road, Changsha, Hunan 410078, China
²Molecular Medical Center, Tongji Hospital, Tongji Medical University, Wuhan 430030, China

Received, Sep 12, 2005; Revised, Sep 26, 2005; Accepted, Oct 15,2005

Correspondence: Ya CAO Tel: +86-731-4805448; Fax: +86-731-4470589; E-mail:ycao98@public.cs.hn.cn

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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 G₂/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G₀/G₁, S and G₂/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.

Keywords: EBV, latent membrane protein 1, cell cycle, G₁/S check point, Survivin, CDK4.