Cab45S和RCN1调控细胞增殖和凋亡的分子机制

项目名称： Cab45S和RCN1调控细胞增殖和凋亡的分子机制

项目编号： No.31471280

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 滕俊琳

作者单位： 北京大学

项目金额： 80万元

中文摘要： 内质网腔内蛋白对维持细胞内稳态起重要作用，然而它们的功能和调控机制很不清楚。Cab45S和RCN1均属于CREC家族蛋白，分别含有5和6个与Ca2+结合的EF-hand结构域。我们前期结果显示Cab45S和RCN1在内质网腔中调控细胞增殖，并且Cab45S与内质网应激诱导的细胞凋亡相关。本项目中，将首先寻找Cab45S和RCN1的相互作用蛋白，分析它们参与调控的相关信号通路。我们将重点关注Cab45S和RCN1在ER膜上的结合蛋白，以及与Ca2+信号通路的关系，探讨它们如何调控细胞内Ca2+平衡，揭示其维持细胞内稳态、调控细胞增殖及内质网应激诱导的细胞凋亡的分子机制。基于Cab45S和RCN1在细胞增殖与凋亡方面的作用，我们还将分析它们与肿瘤生长及发展的关系。本项目的实施将有助于阐明内质网腔内蛋白在维持细胞内稳态、调控细胞增殖及细胞凋亡的分子机制，并且为寻找抗肿瘤药物提供新思路。

中文关键词： 细胞增殖；细胞凋亡；信号通路；分子机制；分子生物学

英文摘要： Endoplasmic reticulum (ER) Luminal proteins play important roles in maintaining cellular homeostasis, but their functions and regulatory mechanisms remain largely unknown. Cab45S and RCN1, belonging to the CREC protein family, are ER luminal proteins that contain 5 and 6 Ca2+ binding EF-hand domains, respectively. Our preliminary results showed that both Cab45S and RCN1 regulated cell proliferation, while Cab45S was also involved in the ER stress-induced apoptosis in the ER lumen. In this project, first, we will screen for their associated proteins and analyze the signaling pathways which they may regulate. Furthermore, we will focus on their interacting proteins in the ER membrane and related Ca2+ signaling pathways, and analyze how Cab45S/RCN1 modulate intracellular Ca2+ homeostasis, to elucidate molecular mechanisms by which Cab45S and RCN1 maintain cellular homeostasis, and regulate cell proliferation/ ER stress-induced apoptosis. Based on the roles of Cab45S/RCN1 in cell proliferation and apoptosis, we will investigate their relationships with tumor growth and progression. The project would facilitate the evaluation of the underlying mechanism of ER lumenal proteins in maintaining cellular homeostasis and regulating cell proliferation and apoptosis, which will provide novel potential therapeutic targets for treating tumors.

英文关键词： cell proliferation;apoptosis;signaling pathway;molecular mechanism;molecular biology