Mechanism of Action LANA Encoded by KSHV

KSHV 编码的 LANA 作用机制

• 批准号: 6450516
• 负责人: ERLE S. ROBERTSON
• 金额: $ 27.22万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6450516
• 关键词: DNA binding protein; Kaposi's sarcoma; acetylation; acyltransferase; affinity chromatography; amidohydrolases; binding sites; clinical research; gene expression; genetic promoter element; genetic regulation; histones; human herpesvirus 8; human subject; latent virus infection; pathologic process; protein protein interaction; protein structure function; virus antigen; virus genetics; virus protein; virus related neoplasm /cancer; yeast two hybrid system

DESCRIPTION (Provided by the applicant): Kaposi's sarcoma herpesvirus (KSHV) is a gammaherpesvirus associated with human malignancies including Kaposi's sarcoma and body cavity based lymphomas (BCBLs) or pleural effusion lymphomas (PELs). One of the latency-associated nuclear antigen (LANA) is constitutively expressed in all latently infected KSHV cells and is involved in the maintenance of the KSHV genome and transcriptional regulation. LANA tethers the KSHV genome to host chromosomes through association with cis-acting DNA element(s) at the left of the viral genome. LANA also associates with chromosomal proteins including histone H 1 potentially tethering the viral genome to host chromosome. There is an increasing body of evidence demonstrating that LANA is critical for KSHV persistence in human malignancies. The specific aims of this proposal are: (1) To investigate the role of LANA in regulating viral and cellular gene expression in KSHV infected growth-transformed cells. (2) To identify and characterize LANA associated proteins and to determine the functional consequences resulting for these specific. (3) To identify additional binding sites for LANA on the KSHV genome and (4) to determine functional domains of LANA which is involved in DNA binding, transcriptional regulation and maintenance of KSHV genome in infected cells. These aims will provide critical information for elucidating the mechanisms by which LANA functions in contributing to KSHV pathogenesis and associated human malignancies.

描述（由申请人提供）：卡波西肉瘤疱疹病毒（KSHV）是 一种与人类恶性肿瘤（包括卡波西氏病）相关的伽玛疱疹病毒 肉瘤和体腔淋巴瘤 (BCBL) 或胸腔积液淋巴瘤 （PEL）。其中一种潜伏相关核抗原 (LANA) 是组成型的 在所有潜伏感染的 KSHV 细胞中表达，并参与 KSHV 基因组的维护和转录调控。 LANA 系绳 KSHV 基因组通过与顺式作用 DNA 关联来宿主染色体 病毒基因组左侧的元件。 LANA 还与 包括组蛋白 H 1 在内的染色体蛋白可能束缚病毒 基因组到宿主染色体。越来越多的证据 证明 LANA 对于 KSHV 在人类恶性肿瘤中的持续存在至关重要。 本提案的具体目标是： (1) 研究 LANA 在 调节 KSHV 感染者的病毒和细胞基因表达 生长转化细胞。 (2) 识别和表征相关 LANA 蛋白质并确定这些蛋白质产生的功能后果 具体的。 (3) 确定 KSHV 基因组上 LANA 的其他结合位点 (4)确定DNA中涉及的LANA的功能域 感染者中 KSHV 基因组的结合、转录调控和维持 细胞。这些目标将为阐明 LANA 在 KSHV 发病机制中发挥作用的机制 相关的人类恶性肿瘤。