Analysis of transcriptional regulator in lymphocyte

cAMP反应元件最初被确定为基因转录调控区域的诱导增强元件，可在cAMP水平升高时转录。另一方面，CRE也可以作为本构增强剂。目前，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结合域（称为B-ZIP结构），并以同二聚体或异二聚体的形式与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小组鉴定的CREB，属于这一组的CREB结合蛋白的反激活能力受到pka依赖性磷酸化的刺激。第二组的典型成员是我们小组鉴定的CRE-BP1， CRE-BP1的反激活能力不受PKA的刺激。CRE- bp1的显著特征是CRE- bp1与c-Jun形成异源二聚体，CRE- bp1 /c-Jun异源二聚体可以与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在细胞内信号转导中cAMP通路和TPA通路的串扰中起着重要作用。

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.