CBP - A SIGNAL-REGULATED TRANSCRIPTIONAL COACTIVATOR CONTROLLED BY NUCLEAR CALCIUM AND CAM KINASE-IV

Recruitment of the coactivator, CREB binding protein (CBP), by signal- regulated transcription factors, such as CREB [adenosine 3',5'-monopho sphate (cAMP) response element binding protein]. is critical for stimu lation of gene expression. The mouse pituitary cell line AtT20 was use d to show that the CBP recruitment step (CREB phosphorylation on serin e-133) can be uncoupled from CREB/CBP-activated transcription. CBP was found to contain a signal-regulated transcriptional activation domain that is controlled by nuclear calcium and calcium/calmodulin-dependen t (CaM) protein kinase IV and by cAMP, Cytoplasmic calcium signals tha t stimulate the Ras mitogen-activated protein kinase signaling cascade or expression of the activated form of Ras provided the CBP recruitme nt signal but did not increase CBP activity and failed to activate CRE B- and CBP-mediated transcription. These results identify CBP as a sig nal-regulated transcriptional coactivator and define a regulatory role for nuclear calcium and cAMP in CBP-dependent gene expression.