Analysis of transcriptional regulator involved in signal transduction in lymphocyte

在众多的CRE（cyclicAMP responseelement）结合蛋白中，CRE-BP 1（也称为ATF-2）具有两个独特的功能：介导腺病毒EIA诱导的反式激活和与c-Jun形成异源二聚体，CRE-BP 1中的金属指和亮氨酸拉链结构是产生这些功能的主要原因。作为具有类似金属指和亮氨酸拉链结构的CRE-BP 1家族的新成员，我们分离了CRE-BPa蛋白的cDNA克隆，该蛋白由508个氨基酸组成，分子量为56，840。CRE-BPa蛋白与CRE-BP 1蛋白在4个区域高度同源，其中2个区域为金属指区或由碱性氨基酸簇和亮氨酸拉链组成的DNA结合区。与CRE-BP 1一样，CRE-BPa与CRE结合的亲和力高于与12-OMICRON-十四烷酰基佛波醇-13-乙酸酯反应元件结合的亲和力，其为同二聚体或CRE-BPa/c-Jun或CRE-BPa/CRE-BP 1异二聚体。然而，使用c-Myb-CRE-BPa融合蛋白，显示CRE-BPa不能介导E1 A诱导的反式激活。在有限数量的细胞系中发现CRE-BPa mRNA的表达，并且在一些细胞系和组织中检测到多种大小的CRE-BPa mRNA种类。CRE-BPa将有助于阐明CRE-E1 A或c-Jun介导的转录激活机制。

Among multiple CRE (cyclic AMP response element) -binding proteins, CRE-BP1 (also designated ATF-2) has two unique characeristics : it mediates the adenovirus EIA-induced trans-activation and forms a heterodimer with c-Jun. Two struc ures, a putative metal finger and a leucine zipper, in CRE-BP1 are responsible for these capacities. As a new member of a CRE-BP1 family that has similar metal finger and leucine zipper structures, we have isolated cDNA clones of CRE-BPa protein consists of 508 amino acids and has a molecular weight of 56,840. CRE-BPa protein is highly homologous with CRE-BP1 in four regions : two of them are the regions containing the putative metal finger or the DNA-binding domain consisting of the basic amino acid cluster and the leucine zipper. Like CRE-BP1, CRE-BPa binds to CRE with higher affinity than to the 12-OMICRON-tetradecanoylphorbol-13-acetate response element as a homodimer or a CRE-BPa/c-Jun or CRE-BPa/CRE-BP1 heterodimer. However, using the c-Myb-CRE-BPa fusion protein, it was shown that CRE-BPa could not mediate the E1A-induced trans-acitivation. Expression of CRE-BPa mRNA was found in a limited number of cell lines, and multiple sizes of CRE-BPa mRNA species were detected in some cell lines and tissues. CRE-BPa will be useful to clarify the mechanism of CRE-mediated transcriptional activation by E1A or c-Jun.