Bannister A J, Oehler T, Wilhelm D, Angel P, Kouzarides T
Wellcome/CRC Institute, University of Cambridge, UK.
Oncogene. 1995 Dec 21;11(12):2509-14.
The CBP protein mediates PKA induced transcription by binding to the PKA phosphorylated activation domain of CREB. Here we show that CBP also stimulates the activity of both c-Jun and v-Jun in vivo. The CREB binding domain of CBP is sufficient to contact to c-Jun in vitro. When this domain of CBP is linked to the activation domain of VP16 and expressed in vivo it stimulates c-Jun dependent transcription. Deletion analysis of c-Jun indicate that the CBP binding site is within the N-terminal activation domain. Loss of binding to CBP in vitro correlates with severely reduced transactivation capacity in vivo. Mutation of Ser63/73 in c-Jun, or the corresponding position in v-Jun (Ser36/46) leads to reduced binding to CBP in vitro and abolishes augmentation of transcription in vivo. These data are consistent with a mechanism by which CBP acts as a co-activator protein for Jun dependent transcription by interacting with the Jun N-terminal activation domain.
CBP蛋白通过与CREB的PKA磷酸化激活结构域结合来介导PKA诱导的转录。在此我们表明，CBP在体内也能刺激c-Jun和v-Jun的活性。CBP的CREB结合结构域在体外足以与c-Jun接触。当CBP的这一结构域与VP16的激活结构域相连并在体内表达时，它能刺激c-Jun依赖性转录。对c-Jun的缺失分析表明，CBP结合位点位于N端激活结构域内。在体外与CBP结合的丧失与体内转录激活能力的严重降低相关。c-Jun中Ser63/73或v-Jun中相应位置（Ser36/46）的突变导致体外与CBP的结合减少，并消除体内转录的增强。这些数据与一种机制相符，即CBP通过与Jun N端激活结构域相互作用，作为Jun依赖性转录的共激活蛋白发挥作用。
