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cAMP反应元件结合蛋白(cAMPresponseelement-bindingproteins,CREB)是一个哺乳动物转录因子家族,通过cAMP反应元件(cAMPresponseelement,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MTCpanel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。
The cAMP response element-binding protein (CREB) is a family of mammalian transcription factors that mediate cAMP and calcium-dependent gene expression through the cAMP response element (CRE). CREB4 is a new member of the CREB transcriptional family. Human tumor MTCpanel results show that CREB4 is expressed in human lung cancer LX-1, colon adenocarcinoma CX-1, prostate cancer PC-3, colon cancer G1-112 and pancreatic cancer G1-103. Construction of pLexA Fusion Plasmid Expressing CREB4-LexA and CREB215 ~ 395aa-LexA The yeast EGY48 strain containing p8opLacZ reporter plasmid was transformed into E.coli BL21 (DE3). The expression of CREB4 protein was determined as a transcriptional activator and N-terminal transcriptional activity was determined. The results of subcellular localization showed that the full-length CREB4 protein was located in the cytoplasm, whereas the CREB41-2755 a protein mutant with the deletion of the C-terminal putative transmembrane domain was transferred to the nucleus. The expression profile of CREB4 protein may play a role in the regulation of gene expression in many human tumors. The putative transmembrane domain of C-terminal is closely related to its transcriptional activation.