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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反应元件最初被鉴定为基因转录调控区中的可诱导增强子元件，其可以响应于增加的cAMP水平而转录。另一方面，CRE也可以充当组成型增强子。迄今为止，许多CRE结合蛋白已通过cDNA克隆得到鉴定。它们都具有由碱性氨基酸簇和亮氨酸拉链组成的DNA结合结构域（所谓的B-ZIP结构），并以同源二聚体或异源二聚体的形式与CRE结合。我们的分析表明，这些CRE结合蛋白可以根据其功能分为两组。一组涉及Montiminy小组鉴定的CREB，属于该组的CREB结合蛋白的反式激活能力受到PKA依赖性磷酸化的刺激。第二组的典型成员是本课题组鉴定的CRE-BP 1，CRE-BP 1的反式激活能力不受PKA的刺激。CRE-BP 1的显著特征是CRE-BP 1与c-Jun形成异二聚体，并且CRE-BP 1/c-Jun异二聚体可以结合CRE。已知c-Jun/c-Fos异二聚体（Ap-1）结合TPA反应元件（TRE）。因此，CRE-BP 1在cAMP途径和TPA途径之间的细胞内信号转导的串扰中起重要作用。