NUCLEAR-PROTEIN CBP IS A COACTIVATOR FOR THE TRANSCRIPTION FACTOR CREB

THE transcription factor CREB binds to a DNA element known as the cAMP -regulated enhancer (CRE)(1-5). CREB is activated through phosphorylat ion by protein kinase A (PKA)(6), but precisely how phosphorylation st imulates CREB function is unknown. One model is that phosphorylation m ay allow the recruitment of coactivators which then interact with basa l transcription factors. We have previously identified a nuclear prote in of M(r) 265K, CBP, that binds specifically to the PKA-phosphorylate d form of CREB(7). We have used fluorescence anisotropy measurements t o define the equilibrium binding parameters of the phosphoCREB:CBP int eraction and report here that CBP can activate transcription through a region in its carboxy terminus. The activation,domain of CBP interact s with the basal transcription factor TFIIB through a domain that is c onserved in the yeast coactivator ADA-1 (ref. 8). Consistent with its role as a coactivator, CBP augments the activity of phosphorylated CRE B to activate transcription of cAM-responsive genes.