STIMULATION OF C-JUN ACTIVITY BY CBP - C-JUN RESIDUES SER63 73 ARE REQUIRED FOR CBP INDUCED STIMULATION IN-VIVO AND CBP BINDING IN-VITRO/

The CBP protein mediates PKA induced transcription by binding to the P KA phosphorylated activation domain of CREB. Here we show that CBP als o stimulates the activity of both c-Jun and v-Jun in vivo. The CREB bi nding domain of CBP is sufficient to contact to c-Jun in vitro. When t his domain of CBP is linked to the activation domain of VP16 and expre ssed in vivo it stimulates c-Jun dependent transcription. Deletion ana lysis of c-Jun indicate that the CBP binding site is within the N-term inal activation domain. Loss of binding to CBP in vitro correlates wit h 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 ill vitro and abolishes augmentation of tran scription 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 IV-terminal activation domain.