Aurka激酶影响泡状棘球蚴生长发育的分子机制

项目名称： Aurka激酶影响泡状棘球蚴生长发育的分子机制

项目编号： No.81471970

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘凡

作者单位： 厦门大学

项目金额： 80万元

中文摘要： 泡状棘球蚴病是一种危害严重的致死性寄生虫病，由泡球蚴在人体内呈肿瘤样浸润迁移生长引起。Aurka是一类高度保守的丝氨酸/苏氨酸蛋白激酶，在细胞分裂中发挥重要作用。我们前期研究发现泡球蚴存在Aurka同源分子，其可与泡球蚴p53的同源分子Emp53结合，而Emp53存在潜在的Aurka磷酸化位点。本项目将以体外泡球蚴培养系统作为实验模型，利用前期建立的lenti-virus基因干扰系统并综合运用细胞、免疫及分子生物学手段，明确泡球蚴Aurka与p53的作用关系，阐明Aurka-p53信号通路关键分子在泡球蚴细胞增殖、分化过程中的作用，分析Aurka对AKT和GSK-3β等激酶的影响，揭示Aurka影响泡球蚴生长发育的分子机制。在此基础上分析Aurka小分子抑制剂作为治疗泡球蚴病候选药物的可行性。本项目将为泡球蚴生长发育的分子机制研究提供新的视野和思路，同时有助于泡球蚴病新药物靶点的发现。

中文关键词： 泡状棘球蚴；Aurka激酶；p53；细胞增殖与分化；分子机制

英文摘要： The invasive growth and metastasis of Echinococcus multilocularis (Em) larval in the host liver cause alveolar echinococcosis (AE), one of the most fatal helminthic infections of humans. Aurka is one member of the highly conserved serine/threonine protein kinase family, which play a crucial role in cell division. In our previous study, we found that Em contains Aurka homologue, which can bind p53 homologue Emp53 in vitro. Emp53 also contains phosphorylation sites of Aurka. In this study, we will use the established in vitro system of Em, in combination of the lenti-virus based RNAi system and molecular biological technics, to confirm the interaction of Aurka and p53 and analyze the role of key molecules involved in Aurka-p53 signaling pathway in regulation of Em cell proliferation and differentiation. The effects of Aurka on protein kinases activities and the underlying mechanism will be identified and characterized. Further, we will analyze the feasibility and validity of Aurka inhibitors as the drug candidates for AE treatment. These results will deep our understanding in the mechanism of Em larval development and offer the opportunities for finding new drug targets.

英文关键词： Echinococcus multilocularis;Aurka;p53;cell proliferation and differentiation;molecular mechanism