REGULATION OF REPLICATION AND LATENCY BY EBV EBNAS

描述：潜伏感染EBV的B细胞系是永生的，可以 无限扩散。EBNA2是一种潜伏蛋白，它是 对于永垂不朽来说是必不可少的。这个项目的长期目标是 了解EBNA2如何有助于B细胞基因的重新编程 EB病毒感染后的表达。EBNA2是一种转录 与细胞DNA结合蛋白CBF1相互作用的反式激活剂。 最近，EBNA2-CBF1相互作用和EBNA2-CBF1相互作用之间存在联系 缺口信号转导。建议在这一观察的基础上 进一步阐明引发该事件的下游信号事件 永生的过程。具体目标是：[1]进一步 通过(I)使用诱变来表征EBNA2反式激活机制 定义CBF1上的EBNA2交互接口和(Ii)检查 EBNA2与细胞转录相互作用的功能后果 各种因素。[2]确定新的CST-1潜伏期蛋白的作用 通过(I)表征体内潜伏期和EBV相关的肿瘤发生 外周血淋巴细胞CST-1mRNA和蛋白的表达及意义 EBV相关肿瘤及(Ii)检测CST-1对Notch的阻断能力 模型分化系统中的信号。[3]描述信号的特征 通过确定CBF1下游事件在转录中的作用 与CBF1和[4]连锁的两个新的细胞蛋白的调节 启动CBF1与CBF1相互作用的结构域的结构研究 Notch和EBNA2。

DESCRIPTION: B cell lines latently infected with EBV are immortal and can proliferate indefinitely. EBNA2 is one of the latency proteins that is essential for immortalization. The long-term goal of this project is to understand how EBNA2 contributes to the reprogramming of B cell gene expression that follows EBV infection. EBNA2 is a transcriptional transactivator that interacts with the cellular DNA binding protein CBF1. Recently, a linkage has been made between the EBNA2-CBF1 interaction and Notch signal transduction. It is proposed to build on this observation to further elucidate the downstream signaling events that initiate the immortalization process. The Specific Aims are: [1] To further characterize EBNA2 transactivation mechanisms by (i) using mutagenesis to define the EBNA2 interaction interface on CBF1 and (ii) examining the functional consequences of EBNA2 interaction with cell transcription factors. [2] To determine the contribution of the new CST-1 latency protein to in vivo latency and EBV-associated tumorigenesis by (i) characterizing CST-1 mRNA and protein expression in peripheral blood lymphocytes and EBV-associated tumors and (ii) testing the ability of CST-1 to block Notch signaling in a model differentiation system. [3] To characterize signaling events downstream of CBF1 by determining the role in transcriptional regulation of two novel cellular proteins that are linked to CBF1 and [4] To initiate structural studies of the domains involved in CBF1 interaction with Notch and EBNA2.