乳腺癌细胞中p27^(kip1)分子相互作用蛋白质谱的改变  

The Cross-talk Between p27^(kip1) and Its Interacting Molecules in Breast Cancer Cells

作　　者：何玮玮[1] 管晓翔[1] 陈龙邦[1] 

机构地区：[1]南京大学医学院临床医学院南京军区南京总医院肿瘤内科,南京210002

出　　处：《生物化学与生物物理进展》2008年第6期637-642,共6页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(30470669).~~

摘　　要：p27kip1是细胞周期重要的负性调控因子,在乳腺癌等多种肿瘤发生发展过程中发挥重要作用.乳腺癌细胞中p27kip1蛋白通常是低丰度表达和错位分布,导致这种分布和表达改变的确切机制并不明确.已有研究表明,p27kip1磷酸化是重要的调节途径之一,细胞内外信号分子通过多种途径调节p27kip1的分布和表达.为了进一步阐明肿瘤细胞内调节p27kip1功能的分子机制,必须首先明确p27kip1在肿瘤细胞与正常细胞中相互作用蛋白质谱的差异.包括细胞周期素、周期素依赖性激酶、CRM1、jab1、Skp2等在内的多种分子可以与p27kip1发生相互作用.在乳腺癌细胞中还有几种特异的作用分子.在不同细胞周期和不同细胞内分布状态下,p27kip1蛋白有不同的相互作用蛋白质谱.因此,我们推断在乳腺癌细胞内p27kip1分子相互作用蛋白质谱的差异可能是导致其低表达和错位分布的主要机制.p27^kip1 is an important negatively regulator of cell cycle progression and plays a central role in the pathogenesis of a member of tumors including breast cancer. In breast cancer cells, the level of p27^kip1 expression usually decreases during tumor development and progression, in addition, cytoplasm mislocalization of p27^kip1 has been reported, but less is known about the exact molecular mechanisms. Studies have indicated that phosphorylation is the key regulation way, several signal transduction pathways are involved in the regulation of the expression and distribution of p27^kip1. To further understand the mechanism, the disparity of the interacting protein profiling between tumor cells and normal cells must be identified first. Including cyclins, cyclin-depend kinases, CRM1, jab1, SKP2, p27^kip1 has various interacting molecules. There are also several interacting molecules especially for breast cancer cells. It seems that different protein profiling cause the different expression and intracellular distribution in different cell cycle phase. So, disparity of the p27^kip1 protein profiling may be the main mechanism of its down-expression and mislocalization in breast cancer cells.

关 键 词：乳腺癌 P27^KIP1 低丰度表达和细胞内错位分布 磷酸化 信号传导途径 相互作用蛋白质谱 

分 类 号：Q7[生物学—分子生物学] R73[医药卫生—肿瘤]