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: 6172881
• 负责人: Clare E Sample
• 金额: $ 23.55万
• 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 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6172881
• 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） 爱泼斯坦 - 巴尔病毒是与 人类癌症，与三个癌症之一 最大的与艾滋病相关的恶性肿瘤。 EBV的能力 转化主要B淋巴细胞可能在发育中发挥作用 这些恶性肿瘤。 目的是确定细胞途径 由六种病毒蛋白之一靶向，证明是必不可少的 转化，EBNA-3A，申请人的初步证据表明 充当转录因子。 具体而言，申请人提出了 至：1）确定EBNA-3A相关蛋白的功能。 初步的 数据表明EBNA-3A至少有两个细胞 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两杂化鉴定 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 极有可能充当转录调节器，影响 有助于EBV介导的转化的细胞基因的表达。 EBNA-3A调节的基因将通过代表性差异确定 分析。 3）确定EBNA-3A功能在 病毒感染的背景。 最后，申请人将确定 那些已经鉴定出的EBNA-3A函数的意义， 以及在本应用程序中要确定的那些，通过生成 重组EBV编码EBNA-3A，突变影响每个人 功能。 通过检查这些重组EBV基因组的能力 永生的原发性人类B淋巴细胞，申请人将确定 给定功能是否有助于EBV介导的转换。 EBNA-3A相关蛋白和EBNA-3A调控基因的鉴定 将确定EBNA-3A靶向的细胞途径。 使用EBNA-3A作为探针的这些途径的分析很可能很可能 不仅可以进一步理解与EBV相关的恶性肿瘤，还可以 增加对可能是细胞增殖的控制的知识 在其他类型的癌症中破坏。