EB病毒特早期蛋白質Rta活化14-3-3 σ表現及其對細胞週期之影響

Abstract

Epstein-Barr virus (EBV) is the etiologic agent responsible for infectious mononucleosis and oral hairy leukoplakia. It is also highly associated with several human malignancies, such as Burkitt’s lymphoma, Hodgkin’s lymphoma and nasopharyngeal carcinoma (NPC). Many researches have suggested that regulation of the cell cycle is one strategy frequently used by viruses to create a more favorable environment for viral replication. From the previous studies of our lab, we have demonstrated that EBV Rta had the ability to block cell cycle at the G1 phase through regulating the expression of p21 protein. Furthermore, data from a cDNA microarray indicated that Rta could upregulate 14-3-3 σ in transcriptional level. The 14-3-3 σ protein is reported to interact with many cell cycle-related molecules. In this study, we intend to elucidate whether Rta activates 14-3-3 σ expression to affect cell cycle progression. First, we confirmed that Rta could upregulate 14-3-3 σ mRNA and protein expression by using RT-Q-PCR and western blotting assay. Moreover, we found that Rta could transactivate the 14-3-3 σ promoter in a manner independent of its putative Rta-responsive element. In addition, we demonstrated that Rta affected the subcellular localization of CDK1 and CDK2 in 293-TREx-Rta cells via the upregulation of 14-3-3σ expression. Finally, we discovered that Rta also was able to interfere with the G2-M phase progression of cell cycle. Taken together, our results clearly suggest that EBV protein Rta acts through the transcriptional induction of 14-3-3 σ, in addition to p21, to influence cell cycle progression.