Erbin介导细胞周期异常与肿瘤发生的关系

项目名称： Erbin介导细胞周期异常与肿瘤发生的关系

项目编号： No.31271440

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 钱露

作者单位： 中国人民解放军军事医学科学院

项目金额： 60万元

中文摘要： Erbin是2000年发现的ErbB2结合蛋白，属LAP家族新成员。它定位于基底膜，调控上皮细胞间连接、维持细胞极性；并作为支架蛋白，在特定条件下,负调控Ras/Raf/ERK，TGFβ-Smads，Nod2/NF-κB细胞信号通路。我们前期研究首次揭示了Erbin有丝分裂依赖的亚细胞动态定位特征和磷酸化修饰现象，提示Erbin在细胞周期中的新功能。初步发现Erbin调节CDKI分子p21和p27的表达，影响细胞G1/S转换；并初步证实Erbin是新的PLK1激酶底物。本项目拟进一步揭示Erbin调控p21和p27表达的分子机制、分析Erbin磷酸化位点、阐明磷酸化Erbin对细胞有丝分裂的调控环节；在此基础上，探讨Erbin介导细胞周期异常与肿瘤发生的关系，希冀鉴定Erbin作为新的抑癌基因的可能性。

中文关键词： Erbin；skp2；Plk1；细胞周期；肿瘤发生

英文摘要： Erbin, belonging to the LAP protein family, was found as a ErbB2-interacting protein in the year 2000. It localizes at the basolateral membrane to regulate cell junctions and polarity in epithelial cells, and serve as a scaffolding protein in centain conditons to negatively control diverse signal pathways, including Ras/Raf/ERK，TGFβ-Smads，Nod2/NF-κB. In our previous study, it was observed that Erbin is phosphorylated and recruited to different subcellular structures during mitotic progression, indicating erbin novel functions in cell cycle. Here, we preliminarily demonstrate that Erbin orchestrates G1/S transition by controlling expression of CDKI molecular, p21 and p27, and show that Erbin is novel substrate for Plk1.Based on these data, our further study will clarify the molecular mechanism of downregulation of p21 and p27 by loss of Erbin, identify the Erbin phosphorylated sites by plk1 and cdk1, and reveal which mitotic events are controlled by Erbin. Finally, the relationship of dysregulation of cell cycle by erbin and tumorigensis will be concluded in our clinical data. In short, we aims to investigate the possibility that Erbin serves as a tumor suppressor.

英文关键词： Erbin；Skp2；Plk1；cell cycle；tumorigenesis