Calmodulin Kinase II Attenuation of Gene Transcription by Preventing cAMP Response Element-binding Protein (CREB) Dimerization and Binding of the CREB-binding Protein

Abstract

Calmodulin Kinase II (CamKII) inhibits the transcription of many CRE-dependent genes, but the mechanism of dominant transcriptional inhibition is unknown. Here we show that phosphorylation of serine 142 in CREB by CamKII leads to dissociation of the CREB dimer without impeding DNA binding capacity. CamKII-modified CREB binds to DNA efficiently as a monomer; however, monomeric CREB is unable to recruit the CREB-binding protein (CBP) even when phosphorylated at serine 133. Thus, CamKII confers a dominant inhibitory effect on transcription by preventing dimerization of CREB, and this mechanism may account for the attenuation of gene expression.