Tat碱性结构域-Bcl-Xs融合蛋白与细胞短暂共培养可诱导细胞程序性死亡  

Heterogenic Bcl-Xs Fused with Tat Basic Domain can Induce Programmed Cell Death after Transient Incubation

作　　者：郭淑贞[1] 陈亚兵[1] 张军[1] 谢小燕 杨海杰[1] 温龙平[1] 夏宁邵[1] 

机构地区：[1]厦门大学肿瘤细胞工程国家专业实验室,厦门361005

出　　处：《中国生物化学与分子生物学报》2000年第5期674-679,共6页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目!( 3 9670 15 9)

摘　　要：艾滋病毒的 Tat蛋白碱性结构域的 1 3个氨基酸的多肽能自主穿越细胞膜并将与之融合表达的其他蛋白带入细胞 .为探讨融合表达的蛋白是否可保持原有的主要生物学功能 ,将 Bcl- Xs蛋白与 Tat碱性结构域在大肠杆菌中融合表达 ,重组蛋白 Tat- Bcl- Xs与 CHO、CNE、Hela和 772 1细胞共温育一段时间后 ,细胞均可见明显生长抑制 ,同时细胞变圆、变小、细胞核收缩 ,并有染色体凝聚、边缘化 ,或细胞核分裂为小核的现象 ,同时出现梯状 DNA,为较典型的细胞程序性死亡 ( PCD)表现 .同时发现放线菌素 D、雷公藤内脂醇与 Tat- Bcl- Xs在诱导细胞 PCD时存在交互作用 .提示Tat- Bcl- Xs蛋白可自主进入细胞内 ,并保持了 Bcl- Xs蛋白的 PCD诱导作用 ,初步证实了利用 Tat碱性结构域进行药物设计的可行性 ,同时也提示 Tat- Bcl-Transmembrane delivery is important for drug using.The 13 amino acid\|length basic domain of Tat protein of human immunodificiency virus(HIV)has an interesting character that it can pass through the cellular membrane independently,and at the same time the heterogenic protein chemical\|coupled with this peptide can be carried into the cell.The recombinant protein included this Tat basic domain can pass through the cell membrane as well.To test if the fused protein can keep its major biology function,the Bcl\|Xs protein was fused with the basic domain of Tat,and its ability to induce apotosis by extracellular treatment was confirmed in four kinds of cell lines.Besides,the significant interaction between Tat\|Bcl\|Xs and actinomycin\|D or troptolide in programmed cell death induction were also observed.These results suggest that Tat\|Bcl\|Xs recombinant protein can be used as a component in cock\|tail tumor therapy scheme.

关 键 词：BCL-XS Tat碱性结构域 药物跨膜运送 细胞凋亡 

分 类 号：R379.9[医药卫生—病原生物学] R914.2[医药卫生—基础医学]