CBP: A Signal-Regulated Transcriptional Coactivator Controlled by Nuclear Calcium and CaM Kinase IV

• DOI: 10.1126/science.281.5382.1505
• Publication Date: 2002-07-27T09:37:56Z
• Authors: Sangeeta Chawla; Giles E. Hardingham; David R. Quinn; Hilmar Bading
• Keywords: Cell Nucleus; Cytoplasm; 0303 health sciences; Models, Genetic; Recombinant Fusion Proteins; Nuclear Proteins; CREB-Binding Protein; Cell Line; Mice; Phosphoserine; 03 medical and health sciences; Genes, Reporter; Calcium-Calmodulin-Dependent Protein Kinases; Cyclic AMP; Animals; Calcium; Calcium Channels; Phosphorylation; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cyclic AMP Response Element-Binding Protein; Calcium-Calmodulin-Dependent Protein Kinase Type 4; Signal Transduction

Recruitment of the coactivator, CREB binding protein (CBP), by signal-regulated transcription factors, such as CREB [adenosine 3′,5′-monophosphate (cAMP) response element binding protein], is critical for stimulation of gene expression. The mouse pituitary cell line AtT20 was used to show that the CBP recruitment step (CREB phosphorylation on serine-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–dependent (CaM) protein kinase IV and by cAMP. Cytoplasmic calcium signals that stimulate the Ras mitogen–activated protein kinase signaling cascade or expression of the activated form of Ras provided the CBP recruitment signal but did not increase CBP activity and failed to activate CREB- and CBP-mediated transcription. These results identify CBP as a signal-regulated transcriptional coactivator and define a regulatory role for nuclear calcium and cAMP in CBP-dependent gene expression.