PDK1调控因子的垂钓鉴定及在白血病发生发展中的作用和分子机制

项目名称： PDK1调控因子的垂钓鉴定及在白血病发生发展中的作用和分子机制

项目编号： No.81470337

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： 陈一鸣

作者单位： 大连医科大学

项目金额： 70万元

中文摘要： PDK1与白血病的发生发展密切相关。然而，PDK1如何被表达调控进而参与白血病发生发展的具体分子机制，仍不明确。前期研究中我们运用新型的启动子垂钓鉴定系统在白血病细胞中成功垂钓出PDK1的启动子结合蛋白RPS3，验证了RPS3在PDK1启动子区的结合，并证实了RPS3对PDK1表达和白血病细胞增殖的调控。本课题将在此基础上运用该垂钓鉴定系统在其它白血病细胞中验证RPS3在PDK1启动子区的结合，研究RPS3对PDK1启动子转录活性的调控以及对白血病细胞增殖、凋亡、迁移和侵袭的影响及其具体分子机制；并进一步研究PDK1和RPS3在不同类型白血病细胞和白血病患者中的表达、二者的相关性及其与白血病分型、分期、预后及转移复发的联系,确定其临床意义。本课题旨在确认RPS3在白血病细胞中对PDK1的转录调控，阐明RPS3参与白血病发生发展的分子机制，以期为白血病的诊断和治疗提供新靶标。

中文关键词： 白血病；丙酮酸脱氢酶激酶同工酶1；启动子；转录因子

英文摘要： PDK1 is closely associated with leukemia. However, how PDK1 is regulated and involved in the development of leukemia and its underlying mechanism remain unknown.In the preliminary studies, we used a novel system to pull down and identify RPS3 as a PDK1 promoter-binding proteins in leukemia cells and found that RPS3 regulated PDK1 expression and tumor cell growth. In this study, we will confirm the binding of RPS3 on PDK1 promoter by the pulldown system, study the regulation of RPS3 in PDK1 promoter activity, cell growth and apoptosis,migration and invision in leukemia cells mcell, thereby identifying the underlying molecular mechanisms. Moreover, we will also analyze PDK1 and RPS3 expression in various leukemia cell liness and patients and evaluate their correlation with leukemia stage, survival,metastasis, recurrence, thereby identifying the clinical implications of RPS3 and PDK1.This program will provide new understanding for identification of the transcriptional regulation of RPS3 on PDK1, elucidate the mechanisms by which RPS3 is involved in leukemia, thereby provide new targets for the diagnosis and therapy for leukemia.

英文关键词： leukemia;PDK1;promoter;transcription factor