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 factors bind to this element, including the protein CREB5,6, which is activated as a result of phosphorylation by protein kinase A7. This modification stimulates interaction with one or more of the general transcription factors or, alternatively, allows recruitment of a co-activator. Here we report that CREB phosphorylated by protein kinase A binds specifically to a nuclear protein of Mr 265K which we term CBP (for CREB-binding protein). Fusion of a heterologous DNA-binding domain to the 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.

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