ROLE OF EBNA-3A IN EBV-MEDIATED B CELL TRANSFORMATION

EBNA-3A 在 EBV 介导的 B 细胞转化中的作用

• 批准号: 2895845
• 负责人: Clare E Sample
• 金额: $ 22.65万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2895845
• 关键词: B lymphocyte; Epstein Barr virus; cell growth regulation; cell transformation; human subject; neoplasm /cancer genetics; tissue /cell culture; transcription factor; viral carcinogenesis; virus genetics; virus protein

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.

描述：（申请人的描述） Epstein-Barr病毒是一种有限数量的病毒， 人类癌症，并与三种癌症之一高度相关， 艾滋病相关恶性肿瘤的最大群体。 EB病毒的能力， 转化的原代B淋巴细胞可能在发展中发挥作用 这些恶性肿瘤。 目的是确定细胞通路 被证明是必不可少的六种病毒蛋白之一所靶向， 转化，EBNA-3A，申请人的初步证据表明， 作为转录因子发挥作用。 具体而言，申请人建议 目的：1）鉴定EBNA-3A相关蛋白的功能。 初步 数据表明，EBNA-3A与至少两种细胞结合， 蛋白质，其中之一是J-kappa转录因子。 未知 EBNA-3A相关蛋白将使用酵母双杂交技术鉴定。 系统 2)鉴定由EBNA-3A调控的细胞基因。 初步 数据以及与其他病毒蛋白的同源性表明，EBNA-3A是 很可能作为转录调节因子发挥作用，影响 有助于EBV介导的转化的细胞基因的表达。 EBNA-3A调节基因将通过代表性差异来鉴定 分析. 3)确定EBNA-3A功能在 病毒感染的背景。 最后，申请人将决定 已经确定的EBNA-3A功能的重要性， 以及在本申请中要识别的那些， 编码EBNA-3A的重组EB病毒，其突变影响每个个体 功能 通过检测这些重组EBV基因组的能力， 永生化原代人B淋巴细胞，申请方将确定 给定的功能是否有助于EBV介导的转化。 EBNA-3A相关蛋白和EBNA-3A调控基因的鉴定 将能够确定EBNA-3A靶向的细胞途径。 使用EBNA-3A作为探针对这些途径进行分析， 不仅加深了对EB病毒相关恶性肿瘤的理解， 增加控制细胞增殖的知识， 在其他类型的癌症中被破坏。