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

• 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

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结合蛋白中，Cre-BP1(又称ATF-2)具有两个独特的特性：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-BP1中的两个结构，一个可能的金属手指和一个亮氨酸拉链，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，我们已分离到Cre-BPA蛋白的cDNA克隆，由508个氨基酸组成，分子量为56,840。Cre-BPA蛋白与Cre-BP1蛋白在四个区域高度同源：其中两个区域含有可能的金属指或由碱性氨基酸簇和亮氨酸拉链组成的DNA结合域。与Cre-BP1类似，Cre-BPA以同源二聚体的形式与Cre结合，而不是以同源二聚体或Cre-BPA/c-jun或Cre-BPA/Cre-BP1异源二聚体的形式与Cre反应元件结合。然而，使用c-Myb-Cre-BPA融合蛋白，发现Cre-BPA不能介导E1a诱导的反式激活。在少数细胞系中发现Cre-BPA mRNA的表达，在某些细胞系和组织中检测到多种大小的Cre-BPA mRNA物种。Cre-BPA有助于阐明E1a或c-jun介导的Cre转录激活机制。

项目成果

Someya,Y.: "Two 3'-5'-cyclic-adenosine monophosphate response elements in the promoter region of the human gastric inhibitory polypeptide gene." FEBS Lett.317. 67-74 (1993)

Someya,Y.：“人胃抑制多肽基因启动子区的两个 3-5-环单磷酸腺苷反应元件。”

Nomura,N.: "Isolation and characterization of a novel member of the gene family encoding the cAMP response element-binding protein CRE-BP1." J.Biol.Chem.268. 4259-4266 (1993)

Nomura,N.：“编码 cAMP 反应元件结合蛋白 CRE-BP1 的基因家族新成员的分离和表征。”

Someya,Y.: "Two 3'-5'-cyclic-adenosine monophosphate response elements in the promoter region of the human gastric inhibitory polypeptide gene." FEBS Lett.317. 67-73 (1993)

Someya,Y.：“人胃抑制多肽基因启动子区的两个 3-5-环单磷酸腺苷反应元件。”

Zu,Y.-L.: "Regulation of trans-activation capacity of CRE-BPa by phorbol ester tumor promoter TPA." Oncogene. 8. 2749-2758 (1993)

Zu,Y.-L.：“佛波酯肿瘤启动子 TPA 对 CRE-BPa 反式激活能力的调节。”