PHOSPHORYLATED CREB BINDS SPECIFICALLY TO THE NUCLEAR-PROTEIN CBP

CYCLIC AMP-regulated gene expression frequently involves a DNA element known as the cAMP-regulated enhancer (CRE)1-4. Many transcription fac tors bind to this element, including the protein CREB5,6, which is act ivated as a result of phosphorylation by protein kinase A7. This modif ication stimulates interaction with one or more of the general transcr iption factors or, alternatively, allows recruitment of a co-activator . Here we report that CREB phosphorylated by protein kinase A binds sp ecifically to a nuclear protein of M(r) 265K which we term CBP (for CR EB-binding protein). Fusion of a heterologous DNA-binding domain to th e amino terminus of CBP enables the chimaeric protein to function as a protein kinase A-regulated transcriptional activator. We propose that CBP may participate in cAMP-regulated gene expression by interacting with the activated phosphorylated form of CREB.