PTPRO通过c-Abl靶定E2F1负调控细胞周期的进程

发布时间：2018-07-10 03:54

本文选题：PTPRO + c-Abl　；参考：《东北师范大学》2011年硕士论文

【摘要】：PTPRO是一种典型的受体型酪氨酸磷酸酯酶,定位于细胞膜,主要参与肾小球的滤过功能,以及神经轴突的生长和导向。在许多肿瘤细胞中,PTPRO由于启动子甲基化而被沉默,还有许多情况染色体该区域是杂合缺失的,说明PTPRO具有抑癌基因的典型特征,过表达的PTPRO在肿瘤细胞中发挥肿瘤抑制因子的功能。目前许多研究表明PTPRO能提高细胞对凋亡的敏感性,抑制细胞非锚定依赖的生长,负调控细胞周期,但是作为跨膜蛋白的PTPRO如何调节细胞周期,其具体机制仍不是十分清楚。c-Abl属于非受体型酪氨酸磷酸激酶家族,是一个多结构域的复杂蛋白。含有核定位信号序列和核输出信号序列,可以在细胞核与细胞质之间穿梭。目前对于c-Abl研究比较清楚的是在DNA损伤反应中,c-Abl入核诱导细胞凋亡,c-Abl也能负调节细胞周期,抑制细胞的生长。本文旨在寻找PTPRO调节细胞周期发挥功能的途径,即从细胞膜到细胞核的一条通路。c-Abl在一定条件下能够核质穿梭,并且对细胞周期有着与PTPRO类似的抑制作用。为了研究c-Abl是否参与了PTPRO对细胞周期的调节,我们在HeLa细胞中发现PTPRO和c-Abl均能下调E2F1,并且通过CoIP证明PTPRO与c-Abl存在于同一沉淀复合物中,免疫荧光和亚细胞抽提结果显示,在一定时间内,PTPRO促进c-Abl的核定位,暗示c-Abl可能在PTPRO调节细胞周期的过程中起到了桥梁作用。本项研究为进一步阐明PTPRO对细胞周期的具体调节机制提供了实验依据。
[Abstract]:PTPRO is a typical receptor tyrosine phosphatase located in the cell membrane, mainly involved in glomerular filtration function, as well as the growth and orientation of nerve axons. In many tumor cells, PTPRO is silenced by promoter methylation, and in many cases this region of chromosome is heterozygous, suggesting that PTPRO has typical characteristics of tumor suppressor gene. Overexpression of PTPRO plays the role of tumor suppressor in tumor cells. At present, many studies have shown that PTPRO can increase the sensitivity of cells to apoptosis, inhibit cell non-anchored growth, and negatively regulate cell cycle. However, as a transmembrane protein, PTPRO regulates cell cycle. Its mechanism is still unclear. C-Abl belongs to the non-recipient tyrosine phosphokinase family and is a complex protein with multiple domains. Nuclear localization signal sequence and nuclear output signal sequence can shuttle between nucleus and cytoplasm. At present, it is clear that c-Abl can also negatively regulate cell cycle and inhibit cell growth in c-Abl damage response. The aim of this study is to find a way for PTPRO to regulate the function of cell cycle, that is, a pathway from cell membrane to nucleus. C-Abl can shuttle nuclear and cytoplasm under certain conditions, and has a similar inhibitory effect on cell cycle. In order to study whether c-Abl is involved in the regulation of cell cycle, we found that both PTPRO and c-Abl can down-regulate E2F1 in HeLa cells. The results of immunofluorescence and subcellular extraction showed that both PTPRO and c-Abl existed in the same precipitate complex. The nuclear localization of c-Abl was promoted by PTPRO for a certain period of time, suggesting that c-Abl may play a role as a bridge in the regulation of cell cycle. This study provides experimental basis for further elucidating the specific regulation mechanism of PTPRO on cell cycle.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363

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