信号通路XBP1-p21在细胞周期调控中的分子机制研究

项目名称： 信号通路XBP1-p21在细胞周期调控中的分子机制研究

项目编号： No.31301119

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 江启慧

作者单位： 重庆大学

项目金额： 20万元

中文摘要： 细胞周期调控因子p21是一个重要的细胞周期蛋白依赖性激酶抑制剂。当细胞损伤时，p21即能阻止变异细胞增殖，诱发细胞凋亡，从而保护机体组织。既往研究表明p21与细胞DNA修复、凋亡以及肿瘤增殖有密切的联系。尽管已发现p53和c-MYC是p21的重要调控因子，但对p21调控的分子机制尚未完全理清。应用shRNA表达文库对p21转录活性进行筛选，我们发现非折叠蛋白应激因子XBP1是一个新的p21转录调控因子。本课题将从以下三方面展开深入研究：(1)解析XBP1对p21的调控机制和细胞功能的影响; (2)阐明XBP1-p21通路与p53、c-MYC信号分子之间的相互作用; (3)考察XBP1-p21通路对肿瘤生长的影响。通过本项研究拟揭示XBP1-p21信号通路的分子调控机制，以加深对细胞功能调控的理解，为与细胞增殖及凋亡相关的疾病治疗提供新的理论依据。

中文关键词： 细胞周期；非折叠蛋白应激因子XBP1；p21；HDM2 (MDM2)；p53

英文摘要： The cyclin-dependent kinase inhibitor p21 is essential in the regulation of cell cycle progression. p21 can inhibit the activity of cyclin-CDK1 and/or -CDK in response to DNA damage stress. p21 mediates G1 phase cell cycle arrest and leads the cells to enter G0 phase，in which cell proliferation and cell cycle are stopped，and the damages are fixed. p21 is also involved in the regulation of apoptosis pathway，a further way to protect the cells when the damages could not be repaired. Thus，p21 is an critical factor for protecting the cells and the whole body by preventing the damaged and/or mutated cells to proliferate. Furthermore，recent reports showed that p21 is also involved in cells senescence and tumor formation. In response to a variety of stresses, tumor suppressor gene p53 and oncogene c-MYC play an important role in regulation of p21 activation. However，the whole mechanism of p21 regulation remains to be elucidated. In an effort to elucidate the mechanism of p21 regulation，in our preliminary experiment，we performed a systematical screening by using shRNA (short hairpin RNA) expression library against transcriptional factors. We discovered a novel p21 regulator，X-box Binding Protein 1 (XBP1). We found that inhibition of XBP1，a factor involved in Unfolded Protein Response (UPR)，significantly upregulated the

英文关键词： cell cycle；XBP1；p21；HDM2 (MDM2)；p53