TRANSACTIVATION OF CD23 BY EBNA-2 AND LMP

EBNA-2 和 LMP 对 CD23 的反激活

• 批准号: 3085879
• 负责人: SO F TSANG
• 金额: $ 7.72万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3085879
• 关键词: B lymphocyte; CD antigens; DNA binding protein; DNA footprinting; Epstein Barr virus; antisense nucleic acid; cell transformation; gene deletion mutation; gene expression; genetic manipulation; genetic transcription; latent virus infection; leukocyte activation /transformation; membrane proteins; molecular cloning; nuclear runoff assay; nucleoproteins; point mutation; tissue /cell culture; transcription factor; transforming virus; virus antigen; virus protein

Epstein-Barr virus (EBV) is a herpes virus which can cause nasopharyngeal carcinoma, African Burkitt's lymphoma, monoclonal and polyclonal lymphoproliferative disorders in immunocompromised host. EBV preferentially infects normal B lymphocytes and results in rapid and efficient transformation of B lymphocytes into immortalized cell lines. Six nuclear proteins: EBNA-1, EBNA-2, EBNA-3A, EBNA-3B, EBNA-3C, EBNA-LP, and one membrane protein LMP; are expressed in latently infected growth- transformed lymphocytes. By genetic analysis, EBNA-2 has been shown to be essential for EBV induced transformation. The exact mechanism by which EBNA-2 contributes to growth transformation is still unknown. EBNA-2 confers a phenotypic change in growth and may function by specifically inducing cellular CD23 gene expression. CD23 was detected on B cell surface within 24 hours after EBV infection. Immortalized B cells arise almost exclusively from CD23 positive cell population. LMP, the latent membrane protein, has direct transforming ability in rodent fibroblast, cooperatively induces CD23 in BJAB cells (EBV negative Burkitt's lymphoma cells). Detailed studies of the transactivation mechanism of cellular CD23 by EBNA-2 and LMP will enable us to understand how these latent genes contribute to B lymphocyte transformation as well as normal B cell growth regulation. Specifically, the goals of this proposal are to determine: (1) the mechanism by which EBNA-2 and LMP induce CD23, (2) the EBNA-2 domains essential for transformation and CD23 transactivation (3) the role of CD23 expression in EBV induced growth transformation, both by overexpression and inhibition of CD23

EB病毒（Epstein-Barr virus，EBV）是一种疱疹病毒，可引起鼻咽炎， 癌，非洲伯基特淋巴瘤，单克隆和多克隆 免疫受损宿主的淋巴组织增生性疾病。 EBV 优先感染正常的B淋巴细胞，并导致快速和 将B淋巴细胞有效转化为永生化细胞系。 6种核蛋白：EBNA-1、EBNA-2、EBNA-3A、EBNA-3B、EBNA-3C、EBNA-LP、 和一种膜蛋白LMP;在潜伏感染的生长中表达- 转化的淋巴细胞 通过遗传分析，EBNA-2已被证明是EBV诱导的细胞凋亡所必需的。 转型 EBNA-2促进生长的确切机制 转型仍是未知数。 EBNA-2赋予细胞表型改变， 可能通过特异性诱导细胞CD 23基因发挥作用 表情 EBV感染后24 h内B细胞表面可检测到CD 23 感染 永生化B细胞几乎完全由CD 23产生 阳性细胞群。 LMP是一种潜在的膜蛋白， 转化能力，协同诱导CD 23， BJAB细胞（EBV阴性伯基特淋巴瘤细胞）。 详细研究 EBNA-2和LMP对细胞CD 23反式激活机制将 使我们能够了解这些潜在的基因如何促进B淋巴细胞 转化以及正常B细胞生长调节。 具体而言，本提案的目标是确定： (1)EBNA-2和LMP诱导CD 23的机制， (2)EBNA-2结构域对转化和CD 23 转录激活 (3)CD 23表达在EBV诱导的生长转化中的作用， 通过过度表达和抑制CD 23