Although LMP1 is expressed in the majority of Nasopharyngeal carcinoma(NPC), the effect of LMP1 on cellular gene expression and its contribution to the cell growth and the development of malignancy is largely unknown.CyclinD1 expression activated by LMP1 was studied.A dual-stable LMP1 integrated NPC cell line with Tet-on regulating system, designated as Tet-on-LMP1 HNE2 was used to gain insight into the cell kinetics of the induction of cyclinD1 with Western blotting. The expression of LMP1 in Tet-on-LMP1-HNE2 was tightly regulated by tetracycline or its derivation, doxycycline. LMP1 has two essential signaling domains with the carboxy terminus, termed C-terminal activation regions1(CTAR1) and CTAR2.With cell lines stably expressed wild type LMP1 , the vector or various deletion mutants and reporter gene assay, the activation essential domains of LMP1 activation cyclinD1 was also identified. The progression of cell cycle was determined by flow cytometry and soft agar assay was done to indicate that the cyclinD1 induced by LMP1 is functional.The results indicates that LMP1 induced cyclin D1 protein expression in both dose-dependent and time-dependent manner with Western blotting analysis in Tet-on-LMP1-HEN2 cell line. Reporter gene assay revealed that wild type LMP1 also can induce cyclinD1 expression at the transcriptional level via trans-activation compared to the control(11.2 fold). LMP1 deletion mutants lacking either CTAR1 or CTAR2 or both the CTAR1 and CTAR2 deletion mutants had a decreased ability to induce cyclin D1 expression(76.4%,19.3%,17.7%).The results of flow cytometry analysis pointed to a cell cycle arrest at the G0/G1 phase compared to doxycycline negative Tet-on-LMP1-HNE2 (66.42% to 56.55%).Compared with cultured with sense PS-ODN-LMP1 (30.48%), cultured with antisense PS-ODN-LMP1 and cyclinD1 showed profound decrease in colony formation(15.21%,21.76%). This is the first report showing that cyclin D1 expression could be activated by a viral protein, LMP-1. This novel finding may thus represent a direct link between LMP1 and cell cycle regulator,CyclinD1.