KSHV (HHV8) KAPOSIN ONCOGENE

KSHV (HHV8) KAPOSIN 癌基因

• 批准号: 6725838
• 负责人: LEONARD J ROSENTHAL
• 金额: $ 11.12万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2004-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6725838
• 关键词: Kaposi's sarcoma; biological signal transduction; calmodulin dependent protein kinase; gene expression; gene mutation; growth factor receptors; human herpesvirus 8; laboratory rabbit; monoclonal antibody; neoplastic transformation; oncogenes; phosphorylation; tissue /cell culture; virus protein; virus related neoplasm /cancer

DESCRIPTION: Human herpesvirus-8 (HHV-8 or KSHV) has been linked to KS and body cavity-based lymphomas. The investigator's laboratory showed that a 60 amino acid kaposin protein encoded by a viral mRNA is expressed in all stages of infection. Kaposin can transform Rat-3 cells in vitro, and the transformed cells caused tumors in nude mice. Therefore, kaposin may play a key role in transformation, and further study of kaposin is important. Four specific aims are proposed. The first is to determine the transforming domains by generating mutant kaposins. The second is to generate kaposin specific monoclonal antibodies to study the expression of kaposin protein in KS and tumor cells. The third aim is to determine the effects of kaposin expression by itself or in combination with other KSHV transforming genes on various endothelial cells and lymphoid cells. The last aim is to determine the mechanism of transformation by focusing on its interaction with growth factor receptors and as a target for phosphorylation by calmodulin-dependent kinase. This study should provide new information on the pathogenesis of HHV-8.

描述：人类疱疹病毒-8（HHV-8或KSHV）与KS有关， 体腔淋巴瘤 研究人员的实验室显示， 由病毒mRNA编码的氨基酸卡泊辛蛋白在所有细胞中表达， 感染的阶段。 Kaposin可以在体外转化Rat-3细胞， 转化的细胞在裸鼠中引起肿瘤。 因此，卡波辛可能发挥 Kaposin在转化中起关键作用，对其进一步研究具有重要意义。 四 提出了具体目标。 首先是确定转化 通过产生突变型卡波激活蛋白。 二是生成卡波辛 特异性单克隆抗体，以研究Kaposin蛋白在 KS和肿瘤细胞。 第三个目的是确定卡波辛的作用 自身表达或与其他KSHV转化基因组合表达， 各种内皮细胞和淋巴细胞。 最后一个目标是确定 通过关注其与增长的相互作用， 因子受体，并作为钙调素依赖性磷酸化的靶点 激酶。 这项研究将提供新的信息的发病机制， HHV-8