Analysis of transcriptional regulator in lymphocyte

淋巴细胞转录调节因子分析

基本信息

批准号：
03670257
负责人：
MAEKAWA Toshio
金额：
$ 1.34万
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：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670257/
关键词：
transcriptional regulators lymphocyte signal transduction HIVー1 エンハンサ-結合蛋白質 HIVーTF1 HIVーEP2

项目摘要

The cAMP response element was originally identified as an inducible enhancer element in the transcriptional regulatory region of the gene which can be transcribed in response to increased cAMP level. On the other hand, CRE can also act as a constitutive enhancer. So far,many CRE-binding proteins have been identified by cDNA cloning. All of them have the DNA-binding domain consisting of a basic amino acid cluster and a leucine zipper(so called B-ZIP structure), and bind to CRE as a homodimer or a heterodimer. Our analyses have indicated that these CRE-binding proteins can be classified into two groups based on their functions. One group involves CREB that was identified by Montiminy's group, and the transactivating capacity of CRE-binding proteins belonging to this group is stimulated by PKA-dependent phosphorylation. The typical member of the second group is CRE-BP1 that was identified by our group, and the transactivating capacity of CRE-BP1 is not stimulated by PKA. The striking feature of CRE-BP1 is that CRE-BP1 forms a heterodimer with c-Jun and that a CRE-BP1/c-Jun heterodimer can bind to CRE. A c-Jun/c-Fos heterodimer(Ap-1)is well known to bind to the TPA response element(TRE). Therefore CRE-BP1 plays an important role for a cross-talk between the cAMP pathway and TPA pathway for intracellular signal transduction.

cAMP响应元件最初被确定为基因转录调节区域中可诱导的增强子元件，可以响应cAMP水平提高而转录。另一方面，CRE也可以充当组成型增强剂。到目前为止，已经通过cDNA克隆确定了许多CRE结合蛋白。它们都具有由碱性氨基酸簇和亮氨酸拉链组成的DNA结合域（所谓的B-ZIP结构），并与CRE结合为同型二聚体或异二聚体。我们的分析表明，这些CRE结合蛋白可以根据其功能将其分为两组。一组涉及由Montiminy组鉴定出的CREB，并且PKA依赖性磷酸化刺激了属于该组的CRE结合蛋白的反式激活能力。第二组的典型成员是由我们组识别出的CRE-BP1，并且PKA不会刺激CRE-BP1的反式激活能力。 CRE-BP1的引人注目的特征是CRE-BP1与C-Jun形成异二聚体，并且CRE-BP1/C-JUN异二聚体可以与CRE结合。众所周知，C-JUN/C-FOS异二聚体（AP-1）与TPA响应元件（TRE）结合。因此，CRE-BP1对于cAMP通路和TPA途径之间的串扰起着重要作用，用于细胞内信号转导。