CBP alleviates the intramolecular inhibition of ATF-2 function.

The transcription factor ATF-2 (also called CRE-BP1), whose DNA-binding domain consists of a basic amino acid cluster and a leucine zipper (b-ZIP) region, binds to the cAMP response element as a homodimer or as a heterodimer with c-Jun. The amino-terminal region of ATF-2 containing the transcriptional activation domain is phosphorylated by stress-activated kinases, which leads to activation of ATF-2. We report here that CBP, which was originally identified as a co-activator of CREB, directly binds to the b-ZIP region of ATF-2 via a Cys/His-rich region termed C/H2, and potentiates trans-activation by ATF-2. The b-ZIP region of ATF-2 was previously shown to interact with the amino-terminal region intramolecularly and to inhibit trans-activating capacity. The binding of CBP to the b-ZIP region abrogates this intramolecular interaction. The adenovirus 13S E1A protein which binds to the b-ZIP region of ATF-2 also inhibited this intramolecular interaction, suggesting that both CBP and 13S E1A share a similar function as positive regulators of ATF-2. We found that the b-ZIP regions of c-Jun and CREB also interact with the C/H2 domain of CBP, suggesting that CBP acts as a regulator for a group of b-ZIP-containing proteins. These results shed light on a novel aspect of CBP function as a regulator for a group of b-ZIP-containing proteins.