FUNCTION OF EBV EBNA-3C IN B CELL IMMORTALIZATION

爱泼斯坦-巴尔病毒是为数不多的与 人类癌症。EB病毒转化原代B淋巴细胞和 建立潜伏感染是任何与EBV相关的 恶毒。我们的长期目标是识别细胞路径 EBNA-3C靶向介导其在EBV诱导中的重要作用 转型。具体来说，我们建议： 1.确定EBNA-3C的转录激活机制。 2.确定EBNA-3C功能在以下背景下的意义 EBV有助于EBNA-3C在EBV介导中的重要作用 转型。我们将评估这些EBNA-3C的意义 我们已经确定的功能，在此确定的 提案，以及在进化过程中被保守的域 人类和灵长类病毒，通过检测突变的EBNA-3C的能力 蛋白质的功能转化。 3.鉴定受EBNA-3C调控的细胞基因。EBNA-3c可能会 调控EBV介导的细胞基因表达 转型。EBNA-3C调节的基因将通过检测 EBNA-3C的靶向和代表性途径已知 差异分析。对这些基因的表征很可能识别出 EBNA-3C功能的细胞效应器。拟议中的实验将 使我们能够确定EBNA-3C的靶向细胞通路，从而 它对EBV介导的转化的独特贡献。对这些问题的分析 使用EBNA-3C作为探针的通路不仅很有可能进一步 我们对EBV相关恶性肿瘤的了解，也增加了我们的 对可能被破坏的细胞增殖控制的知识 在其他类型的癌症中。

Epstein-Barr virus is one of a limited number of viruses associated with human cancers. The ability of EBV to transform primary B lymphocytes and establish a latent infection is a prerequisite to any EBV-associated malignancy. Our long-term objective is to identify the cellular pathways targeted by EBNA-3C that mediate its essential role in EBV-induced transformation. Specifically, we propose to: 1. Identify the mechanisms of transcriptional activation by EBNA-3C. 2. Determine the significance of EBNA-3C function within the context of EBV contributes to EBNA-3C's essential role in EBV-mediated transformation. We will evaluate the significance of those EBNA-3C functions that we have already identified, those identified in this proposal, as well as domains that have been conserved during evolution of human and primate viruses, by examining the ability of mutant EBNA-3C proteins to function transformations. 3.Identify cellular genes regulated by EBNA-3C. EBNA-3c is likely to regulate expression cellular genes that contribute to EBV-mediated transformation. EBNA-3C-regulated genes will be identified by examining pathways EBNA-3C is known to target as well as by representational difference analysis. Characterization of these genes is likely to identify cellular effectors of EBNA-3C function. The proposed experiments will enable us to determine the cellular pathways targeted by EBNA-3C and thus its unique contribution to EBV-mediated transformation. Analysis of these pathways using EBNA-3C as a probe, is highly likely to not only further our understanding of EBV-associated malignancies, but also increase our knowledge of the control of cellular proliferation that may be disrupted in other types of cancers.