CREB4基因的表达谱分析和功能初步研究(英文)  

Expression Pattern and Preliminary Functional Analysis of Human CREB4 Gene

作　　者：高永娟[1] 曹根涛 殷刚[3] 王鑫[1] 季朝能[3] 顾少华[3] 倪晓华[1] 

机构地区：[1]华东师范大学生命科学院生物化学及分子生物学实验室,上海200062 [2]上海新智生物技术有限公司,上海200031 [3]复旦大学生命科学院遗传所遗传工程国家重点实验室,上海200433

出　　处：《Acta Genetica Sinica》2005年第9期898-902,共5页

基　　金：青年科技创新项目(编号:53201023)资助~~

摘　　要：cAMP 反应元件结合蛋白(cAMP response element-binding proteins,CREB)是一个哺乳动物转录因子家族,通过cAMP 反应元件(cAMP response element,CRE)介导cAMP和钙离子依赖性基因表达.CREB4是CREB转录家族的新成员.人肿瘤MTC panel结果显示,CREB4在人肺癌LX-1、结肠腺癌CX-1、前列腺癌PC-3、结肠癌G1-112和胰腺癌G1-103中有表达.构建表达CREB4-LexA和CREB215～395aa-LexA的pLexA融合质粒分别转化含p8opLacZ报告质粒的酵母EGY48菌株,诱导表达后发现CREB4蛋白为转录激活因子,N端决定其转录激活活性.亚细胞定位结果显示,全长CREB4蛋白定位于细胞质,而缺失C端假定转膜结构域的CREB41～275aa蛋白突变体则转移至细胞核内.表达谱结果显示CREB4蛋白可能在人多种肿瘤组织的基因表达调控中起作用,其C端假定的转膜结构域与其转录激活功能密切相关.cAMP response element-binding （CREB） proteins are a family of mammalian transcription activators that mediate cAMP and calcium-dependent gene expression through the cAMP response element （CRE）. CREB4 is a novel member of the human CREB family. RT-PCR showed CREB4 transcripts were found in lung carcinoma LX-1, colon adenocarcinoma CX-1, prastatic adenocarcinoma PC-3, colon carcinoma G1-1 12, and pancreatic adenocarcinoma G1-103. Constructing CREB4 and CREB^215-395aa fusion protein with the entire prokaryotic LexA protein respectively disclosed that CREB4 protein functioned as a transcription activator and its Nterminal accounted for the activation ability. Furthermore,a fusion protein of GFP and full-length CREB4 was localized in cytoplasm,whereas the fusion protein of GFP and a deletion mutant lacking the C-terminal putative transmembrane domain was translocated in nucleus. Our results suggested that putative transmembrane domain of CREB4 protein was associated with modulation of its function for the transcriptional activation.

关 键 词：CREB4 人肿瘤MTC panel 转录激活因子 亚细胞定位 基因表达调控 表达谱分析 response element 结合蛋白 

分 类 号：R73-3[医药卫生—肿瘤]