Analysis of transcriptional regulator involved in signal transduction in lymphocyte

淋巴细胞信号转导相关转录调控因子分析

基本信息

批准号：
05670313
负责人：
MAEKAWA Toshio
金额：
$ 1.28万
依托单位：
The Institute of Physical and Chemical Research (RIKEN)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670313/
关键词：
transcriptional regulators lymphocyte signal transduction CRE Cキナーゼ E1A

项目摘要

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.

在多种CRE（环AMP反应元件）结合蛋白中，CRE-BP1（也称为ATF-2）具有两个独特的特性：它介导腺病毒EIA诱导的反式激活并与c-Jun形成异二聚体。 CRE-BP1 中的两种结构（假定的金属指和亮氨酸拉链）负责这些能力。作为具有相似金属指和亮氨酸拉链结构的CRE-BP1家族的新成员，我们分离得到了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蛋白在四个区域中与CRE-BP1高度同源：其中两个是含有假定的金属指或由碱性氨基酸簇和亮氨酸拉链组成的DNA结合结构域的区域。与 CRE-BP1 类似，CRE-BPa 以同二聚体或 CRE-BPa/c-Jun 或 CRE-BPa/CRE-BP1 异二聚体形式与 CRE 结合，其亲和力高于与 12-OMICRON-十四烷酰佛波醇-13-乙酸酯响应元件的亲和力。然而，使用c-Myb-CRE-BPa融合蛋白，表明CRE-BPa不能介导E1A诱导的反式激活。在有限数量的细胞系中发现了 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 E1A 或 c-Jun 介导的 CRE 转录激活机制。