Regulation of transcription factors by protein-protein interaction

许多转录因子的活性受蛋白质-蛋白质相互作用的调节。我们研究了蛋白质-蛋白质相互作用对转录因子的调控。重点介绍了以下参与细胞生长调控的转录因子。Cre(cAMP反应元件)结合蛋白Cre-BP1我们先前通过克隆的方法鉴定了Cre结合蛋白Cre-BP1。Cre-BP1与Cre以同源二聚体或异源二聚体与c-jun结合。我们通过克隆获得了Cre-Bp1相关蛋白Cre-BPA。Cre-BPA与c-Jun或Cre-BP1形成同源二聚体或异源二聚体，并与Cre结合。有趣的是，TPA刺激了Cre-BPA的反式激活能力。Myb原癌基因产物(Myb)我们发现Myb的活性受到位于Myb分子中间的亮氨酸拉链基序的负调控。这表明，一种抑制剂通过这种无色拉链与Myb结合，并阻止其活性。我们已经鉴定出两种蛋白，90 kDa和130 kDa蛋白，可以与Myb Leucien拉链结合。我们还发现Myb可以通过亮氨酸拉链形成二聚体，而Myb二聚体不能与DNA结合，这表明Myb本身也可以起到抑制作用。

Activity of many transcription factors are regulated by protein-protein interaction. We have investigated the regulation of transcription factors by protein-protein interaction. Especially, the following transcription factors that are involved in cellular growth control were focused.1. CRE(cAMP response element)-binding protein CRE-BP1.We previously indentified the CRE-binding protein CRE-BP1 by cDNA cloning. CRE-BP1 binds to CRE as a homodimer or heterodimer with c-Jun. We have indentified the CRE-BP1-related protein CRE-BPa by cDNA cloning. CRE-BPa forms a homodimer or a heterodimer with c-Jun or CRE-BP1, and binds to CRE.Interestingly, the trans-activating capacity of CRE-BPa was stimulated by TPA treatment.2. myb proto-oncogene product (Myb)We have found that the activity of Myb is negatively regulated by the leucine zipper motif located in the middle of Myb molecule. This suggests that an inhibitor binds to Myb through this leucien zipper and blocks its activity. We have identified two proteins, 90- and 130kDa proteins, that can bind to the Myb leucien zipper. We have also found that Myb can form a dimer through the leucine zipper and a Myb dimer cannot bind to DNA.This indicates that Myb itself also can function as an inhibitor.