SND1蛋白与PML蛋白相互作用在APL中促进白血病细胞增殖和抑制分化作用机制的研究

项目名称： SND1蛋白与PML蛋白相互作用在APL中促进白血病细胞增殖和抑制分化作用机制的研究

项目编号： No.31200575

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物物理、生化与生物分子学、生物力学与组织工程

项目作者： 支蕾

作者单位： 天津医科大学

项目金额： 23万元

中文摘要： 急性早幼粒细胞白血病（APL）是一种特殊类型的急性髓系白血病，由于15，17号染色体易位出现了PML-RARα或RARα-PML融合蛋白，使得PML功能丧失，髓系细胞的分化阻滞并无限增殖，导致APL的发生。有文献报道STAT6能负性调控PML的表达。本课题组前期研究发现SND1存在于STAT6转录复合物中，通过连接RNA聚合酶Ⅱ增强STAT6的转录活性。本课题组也发现SND1与白血病细胞的增殖分化相关，并与增殖和分化相关分子PML之间存在负性调控的关系。本项目将以白血病细胞为研究对象，分析SND1对APL细胞增殖和分化的作用及其分子途径。采用特异性shRNA干扰或过表达观察SND1对白血病细胞增殖和分化的影响；用免疫共沉淀和ChIP等方法观察SND1与PML的相互作用；用多色荧光标志观察SND1及及其复合物在细胞内的定位。以SND1为切入点，探求控制白血病细胞增殖和分化障碍的治疗新策略。

中文关键词： PML；增殖；分化；；

英文摘要： Acute promyelocytic leukemia (APL), which is a special type of acute myeloid leukemia, is characterized by t (15;17) translocation leading to the formation of the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) or RARα-PML fusion protein. The resulting fusion protein leads to loss of PML. The loss of PML was found to result in a resistance to apoptosis,increased cellular growth rates, a block in myeloid cell differentiation and leukemogenesis. It has been reported that STAT6 can negatively regulate the expression of PML. Our preliminary studies showed that SND1 exists in STAT6 transcript complexes, and enhances STAT6 transcriptional activity through the RNA polymerase II. Preliminary study of our group also showed that SND1 may enhance proliferation and inhibit differentiation of APL leukemia cells, and negatively regulate the proliferation and differentiation-related molecules-PML. In this project, we choose leukemia cells to explore the effect of SND1 on proliferation and differentiation of APL cells and molecular pathways. We utilize techniques of interference with specific shRNA or overexpression of SND1 to measure the influence of SND1 on proliferation and differentiation of leukemia cells; Co-Immunoprecipitation and ChIP to observe the interaction between SND1 and PML; multicolor fluorescent lab

英文关键词： PML；proliferation；differetiation；；