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首页> 外文期刊>Chinese science bulletin >Regulation of c-Jun/JunB heterodimers mediated by Epstein-Barr virus encoded latent membrane protein 1 on p16
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Regulation of c-Jun/JunB heterodimers mediated by Epstein-Barr virus encoded latent membrane protein 1 on p16

机译:爱泼斯坦-巴尔病毒编码的潜伏膜蛋白1介导的c-Jun / JunB异二聚体对p16的调节

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Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is considered as the major on-cogenic 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.
机译:爱泼斯坦-巴尔病毒(EBV)编码的潜伏膜蛋白1(LMP1)被认为是EBV编码蛋白的主要致癌蛋白,它可以激活包括激活蛋白1(AP-1)在内的许多转录因子。转录因子通过与靶基因启动子结合,反式激活靶基因的转录,调节靶基因的表达等方式在生物学效应中发挥作用。最近,我们发现LMP1可以介导c-Jun和JunB的新异二聚体形式,可以与AP1 DNA序列结合。在本报告中,我们使用生物信息学证实了p16是c-Jun / JunB的假定靶基因。我们使用Tet-on-LMP1 HNE2细胞系作为细胞模型,这是一个双稳态LMP1整合的HNE2细胞系,LMP1的表达可能受Tet系统调控,我们想探讨c-Jun / JunB LMP1介导的异二聚体可以调控p16。数据表明,由LMP1介导的c-Jun / Jun B异二聚体下调了启动子活性和p16表达,并加速了细胞周期进程。这些发现建立了AP-1信号通路与细胞周期之间的新直接联系,并为致癌机理提供了新模型。

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