Regulation of c-Jun/JunB heterodimers mediated by Epstein-Barr virus encoded latent membrane protein 1 on p16

Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered as the major oncogenic protein of EBV encoded proteins, which could transactivate many transcription factors including activator protein 1 (AP-1). Transcription factor plays its role in biological effects through binding to the target gene promoter, transactivating the transcription of target gene, regulating the target gene expression, etc. Recently, we found that LMP1 could mediate a new heterodimer form of c-Jun and JunB, which could bind to AP1 DNA sequence. In this report, we confirmed p16 as a putative target gene of c-Jun/JunB using bioinformatics. We used Tet-on-LMP1 HNE2 cell line as a cell model, which is a dual-stable LMP1 integrated HNE2 cell line and the expression of LMP1 could be regulated by the Tet system, and we wanted to explore whether c-Jun/JunB heterodimers mediated by LMP1 could regulate p16. Data demonstrated that c-Jun/Jun B heterodimers mediated by LMP1 downregulated both the promoter activity and p16 expression, and accelerated the cell cycle progression. These findings established a new direct connection between the AP-1 singnal pathway and the cell cycle, and provided a new model for the carcinogenesis mechanism.