EBNA3C and tumor supressors

EBNA3C 和肿瘤抑制因子

• 批准号: 7756469
• 负责人: ERLE S. ROBERTSON
• 金额: $ 31.77万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-16 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7756469
• 关键词: Acetylation; Acetylesterase; Acquired Immunodeficiency Syndrome; Adult; Adult Hodgkin' s Lymphoma; Affect; Antigens; B-Cell Lymphomas; B-Lymphocytes; BK Virus; Binding; Biochemical; Biological Assay; Biology; Burkitt Lymphoma; Cell Cycle; Cell Cycle Progression; Cell Cycle Regulation; Cell Line; Cell Proliferation; Cell Survival; Cells; Complement; Complex; Cyclin D1; Data; Disease; E2F transcription factors; EP300 gene; Episome; Epstein-Barr Virus Nuclear Antigens; Event; Gene Expression; Genes; Genome; Goals; HIV; HIV Seropositivity; Human; Human Herpesvirus 4; Human Papillomavirus; Human Virus; Immune; Immunocompromised Host; In Vitro; Individual; Infection; Infectious Mononucleosis; Laboratories; Lead; Link; Lymphoproliferative Disorders; Maintenance; Malignant Neoplasms; Modeling; Modification; Molecular Biology; Molecular Genetics; Mutation; Nasopharynx Carcinoma; Nuclear Antigens; Oncogenic Viruses; Patients; Phenotype; Phosphorylation; Phosphorylation Site; Phosphotransferases; Polyomavirus; Population; Post-Translational Protein Processing; Protein p53; Rat-1; Recombinants; Recruitment Activity; Regulation; Retinoblastoma; Retinoblastoma Protein; Role; Simian virus 40; Site; T-Cell Lymphoma; TP53 gene; Testing; Transcriptional Regulation; Transplant Recipients; Transplantation; Tumor Suppressor Proteins; Ubiquitination; Viral; Viral Antigens; Virus; Western Blotting; cell transformation; chromatin remodeling; infected B cell; lymphoblastoid cell line; mutant; prevent; promoter; role model; therapeutic target; tumor; tumorigenesis; young adult

Epstein‐Barr virus (EBV) is a ubiquitous human virus infecting greater than 95% of the adult population. Infection with EBV typically leads to infectious mononucleosis in young adults and results in a lifelong infection. EBV is also associated with a number of human cancers which include Burkitt’s lymphoma, nasopharyngeal carcinoma, Hodgkin’s lymphoma, adult T‐cell lymphomas and lymphoproliferative diseases in immunocompromised transplant (PTLD) and HIV positive AIDS patients (ALD). In vitro, EBV can transform human primary B‐cells in vitro which results in perpetual proliferation of the primary cells into transformed lymphoblastoid cell lines (LCLs). These nascently infected B lymphocytes express a select set of latent genes one of which is the Epstein‐Barr nuclear antigen (EBNA) 3C essential for B cell transformation. The overall goals of this application is to characterize the involvement of EBNA3C with the well known tumor suppressor p53 and to determine the post translational modifications necessary for regulation of p53 which is induced by its interaction with EBNA3C. These studies are the first to directly testing the cooperation of p53 and an essential EBV nuclear antigen EBNA3C.

Epstein-巴尔病毒（EBV）是一种普遍存在的人类病毒，感染超过95%的成年人群。EBV感染通常导致年轻人的传染性单核细胞增多症，并导致终身感染。EBV还与许多人类癌症相关，包括伯基特淋巴瘤、鼻咽癌、霍奇金淋巴瘤、成人T细胞淋巴瘤和免疫功能低下移植（PTLD）和HIV阳性AIDS患者（ALD）中的淋巴组织增生性疾病。在体外，EBV可以在体外转化人原代B-细胞，导致原代细胞永久增殖为转化的淋巴母细胞系（LCL）。这些新生感染的B淋巴细胞表达一组选定的潜伏基因，其中之一是B细胞转化所必需的Epstein-巴尔核抗原（EBNA）3C。本申请的总体目标是表征EBNA 3C与众所周知的肿瘤抑制因子p53的参与，并确定由其与EBNA 3C的相互作用诱导的p53调节所必需的翻译后修饰。这些研究首次直接测试了p53和EBV必需核抗原EBNA 3C的合作。