Analysis of transcriptional regulator in lymphocyte

CAMP反应元件最初被认为是该基因转录调节区中的一个可诱导的增强子元件，它可以转录以响应cAMP水平的升高。另一方面，Cre也可以作为一种结构性增强剂。到目前为止，已有许多Cre结合蛋白通过克隆获得。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类。其中一组涉及Montiminy等人发现的CREB，属于这一组的CRE结合蛋白的反式激活能力通过PKA依赖的磷酸化来刺激。第二组的典型成员为本课题组发现的Cre-BP1，其反式激活能力不受PKA的刺激。Cre-BP1的显著特征是Cre-BP1与c-Jun形成杂二聚体，并且Cre-BP1/c-Jun杂二聚体可以与Cre结合。众所周知，c-jun/c-Fos异源二聚体(AP-1)与TPA反应元件(TrE)结合。因此，Cre-BP1在cAMP途径和TPA途径之间的信号转导中起着重要的作用。

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.