利用四环素调控系统研究CHIP对TGF-β信号通路的抑制性调节  

Tetracycline Controlled CHIP Expression Inhibits TGF-β Signal Pathway

作　　者：徐夏莲[1] 辛宏[1] 张新军[1] 任芳丽[1] 王银银[1] 常智杰[1] 

机构地区：[1]清华大学生物科学与技术系,清华大学生命科学与医学研究院,北京100084

出　　处：《生物化学与生物物理进展》2005年第6期557-561,共5页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(30470888);国家重点基础研究发展规划项目(973)(2001CB510006;2002CB51300);裕元基金资助项目(20240005-06)~~

摘　　要：为了研究伴侣分子相互作用蛋白CHIP对TGF-β信号通路的调控,利用四环素基因表达调控系统,建立四环素调控表达CHIP的稳定细胞系(Mv1Lu-Tetoff-CHIP).利用此细胞模型,发现CHIP的过量表达可显著降低细胞内Smad2/3蛋白水平;荧光素酶报告分析也表明开启CHIP蛋白表达可明显降低Smads介导的基因转录活性;进一步的免疫印迹结果显示CHIP蛋白可明显下调TGF-β所诱导的下游基因JunB的表达.上述结果提示CHIP可以作为一种新的蛋白质分子抑制性调节TGF-β信号通路.To investigate the regulatory function of chaperone interacting protein CHIP in TGF-β signal pathway, a tetracycline induced CHIP expression stable cell line (Mv1Lu-Tet off-CHIP) was generated. In this cell line model, it was observed that overexpression of CHIP dramatically reduced the endougenous Smad2/3 protein level. Luciferase reporter analysis showed that CHIP inhibited the Smads induced transcription activity. Furthermore, Western blot results indicated that CHIP could downregulate gene expression of JunB, a quick response gene induced by TGF-β. These results provided new evidences that CHIP might be a novel signal protein negatively regulating TGF-β signal pathway.

关 键 词：四环素调控 CHIP TGF-Β SMAD2/3 JUNB 抑制 

分 类 号：R735[医药卫生—肿瘤]