TOPK在凋亡素肿瘤选择性凋亡诱导效应中的作用及意义的研究

项目名称： TOPK在凋亡素肿瘤选择性凋亡诱导效应中的作用及意义的研究

项目编号： No.81503105

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 袁萍

作者单位： 华中科技大学

项目金额： 17.9万元

中文摘要： 凋亡素能选择性诱导肿瘤细胞凋亡、对正常细胞没有影响，是很有希望的抗肿瘤制剂。凋亡素在肿瘤细胞中被磷酸化修饰是其发挥作用的关键，确定肿瘤特异性凋亡素激酶不仅有助于诠释凋亡素的“肿瘤选择性”，也有助于揭示肿瘤发生的奥秘。TOPK是新近发现的MAPKK样丝/苏氨酸激酶，具有肿瘤高表达、正常组织严格限制表达的特性。本课题组预实验发现：活化的TOPK能磷酸化纯化的凋亡素蛋白；特异性沉默SGC7901细胞中TOPK，能显著降低凋亡素抑制SGC7901增殖的效率。结果提示TOPK有可能是凋亡素的激酶。本项目拟明确TOPK对凋亡素的磷酸化修饰、并阐明其在凋亡素选择性诱导肿瘤细胞凋亡中的意义。本研究将证实肿瘤特异性凋亡素激酶的存在，从而更好地揭示凋亡素作用机制和促进抗肿瘤制剂的研发，还有助于推动肿瘤发生机制和抗肿瘤药物靶点的研究。

中文关键词： 凋亡素；TOPK；细胞凋亡；蛋白激酶

英文摘要： Apoptin selectively induces tumor cell apoptosis, without influence on normal cells, which is regarded as a potential anti-tumor agent. Phosphorylation of Apoptin in tumor cells is essential for its action. Testifying the tumor specific apoptosis kinase will not only help to explain the mechanism of apoptin, but also promote the research of unknown event in the tumorigenesis. TOPK is a newly discovered MAPKK-like serine/threonine kinase, which is highly expressed in multiple tumors; but strictly controlled in normal tissues. Our previous in vitro kinase assay showed that TOPK can phosphorylate apoptin by in vitro kinase assay. Silencing TOPK by lentivirus could decrease the growth-inhibiting effect of apoptin in SGC7901 cell. These data clued that TOPK might be a tumor specific apoptin kinase. This project will testify that TOPK is a apoptin kinase, and clarify the significance of TOPK-catalized apoptin phosphorylation in the tumor selective apoptosis inducing effect of it. This research will explain the mechanism of apoptin and promote the antitumor agent based on apoptin, it also promotes the research of tumorigenesis and searching specific anti-tumor target.

英文关键词： Apoptin;TOPK;apoptosis;protein kinase