p53靶基因Rap2B对肿瘤细胞骨架的调节作用及其分子机制

申请者利用Mdm2 微阵列芯片筛选p53靶基因时发现Rap2B基因。该基因在肿瘤发生发展中的作用未见报道。预实验结果提示，Rap2B可能通过调节肿瘤细胞骨架蛋白，改变细胞形态，从而促进细胞迁移。.有鉴于此，本项目将在细胞水平研究Rap2B对细胞微管、微丝的聚合及解聚作用的影响，以及对细胞骨架蛋白（Cdc42，Rac，Rho）的调节作用；在分子水平研究Rap2B是否通过其下游特异性效应因子TNIK与PARG调节细胞骨架，及其具体机制。以期揭示Rap2B与肿瘤发生发展的关系，为筛选抗肿瘤靶点提供理论依据。

We identified Rap2B by analyzing a p53 target gene expression microarray database, but little is known about the role of Rap2B in tumor development and tumorigenesis. Our previous experimental results suggest that, Rap2B has a central role in regulating cellular migration, and proposed the mechanism of Rap2B exerting its pro-migration function through its interaction with cytoskeletal proteins.. In this project, at cellular level, we will study the effect of Rap2B in the polymerization and depolymerization of microtubule and actin filaments, and the regulation of Rap2B to cytoskeletal proteins such as Cdc42，Rac，Rho; At molecular level, we will study whether Rap2B can regulate tumor cytoskeleton through its downstream specific effect factors TNIK and PARG, and related mechanism research. We expect our research will uncover the role of Rap2B in tumor development, and will offer another point for potential cancer therapeutic intervention.