EBNA 3A AND EBV MEDIATED B CELL TRANSFORMATION

描述：(申请人描述) 爱泼斯坦-巴尔病毒是为数不多的与 人类癌症，与这三种癌症中的一种高度相关 艾滋病相关恶性肿瘤的最大群体。EB病毒感染的能力 转化原代B淋巴细胞可能在发育中发挥作用 这些恶性肿瘤中。其目的是确定细胞路径 以六种病毒蛋白中的一种为靶点 申请人S的初步证据表明，其转化为EBNA-3A 起转录因子的作用。具体来说，申请人提出了 目的：1)鉴定EBNA-3A相关蛋白的功能。初步 数据显示EBNA-3A与至少两个细胞 蛋白质，其中之一是J-kappa转录因子。未知的事物 EBNA-3A相关蛋白(S)将用酵母双杂交进行鉴定 系统。2)确定受EBNA-3A调控的细胞基因。预赛 数据以及与其他病毒蛋白的同源性表明，EBNA-3A是 极有可能作为转录调节因子发挥作用，影响 有助于EBV介导性转化的细胞基因的表达。 EBNA-3A调控的基因将通过代表性差异进行识别 分析。3)确定EBNA-3A功能在 病毒感染的背景。最后，申请者将决定 已经确定的那些EBNA-3A功能的意义， 以及要在此应用程序中标识的内容，方法是生成 编码EBNA-3A的重组EBV具有影响每个个体的突变 功能。通过检测这些重组EBV基因组的能力 使原代人类B淋巴细胞永生，申请者将决定 给定的函数是否有助于EBV介导的转换。 EBNA-3A相关蛋白及其调控基因的鉴定 将能够确定EBNA-3A靶向的细胞通路。 使用EBNA-3A作为探针对这些途径进行分析，很有可能 不仅加深了对EBV相关恶性肿瘤的认识，而且 增加对控制细胞增殖的知识，这可能是 在其他类型的癌症中表现不佳。

DESCRIPTION: (Applicant's Description) Epstein-Barr virus is one of a limited number of viruses associated with human cancers and has a high degree of association with one of the three largest groups of AIDS-related malignancies. The ability of EBV to transform primary B lymphocytes is likely to play a role in the development of these malignancies. The objective is to determine the cellular pathways targeted by one of the six viral proteins demonstrated to be essential for transformation, EBNA-3A, that the applicant s preliminary evidence suggests functions as a transcription factor. Specifically, the applicant proposes to: 1) Identify the function of EBNA-3A associated proteins. Preliminary data demonstrates that EBNA-3A associates with at least two cellular proteins, one of which is the J-kappa transcription factor. The unknown EBNA-3A-associated protein(s) will be identified using the yeast two-hybrid system. 2) Identify cellular genes regulated by EBNA-3A. The preliminary data, as well as homology to other viral proteins, suggests that EBNA-3A is highly likely to function as a transcriptional regulator, affecting expression of cellular genes that contribute to EBV-mediated transformation. EBNA-3A-regulated genes will be identified by representational difference analysis. 3) Determine the significance of EBNA-3A function within the context of viral infection. Lastly, the applicant will determine the significance of those EBNA-3A functions that have already been identified, as well as those to be identified in this application, by generating recombinant EBV encoding EBNA-3A with mutations affecting each individual function. By examining the ability of these recombinant EBV genomes to immortalize primary human B lymphocytes, the applicant will determine whether a given function contributes to EBV-mediated transformation. Identification of EBNA-3A-associated proteins and EBNA-3A regulated genes will enable determination of the cellular pathways targeted by EBNA-3A. Analysis of these pathways, using EBNA-3A as a probe, is highly likely to not only further the understanding of EBV- associated malignancies, but also increase the knowledge of the control of cellular proliferation that may be disrupted in other types of cancers.