The ATF/CREB family consists of transcription factors that function through binding to the cAMP responsive element (CRE) palindromic octanucleotide, TGACCTCA, a sequence present in many viral and cellular promoters. The best characterized members of this gene family include CREB-1, CREB-2, ATF-1, ATF-2, ATF-3 and ATF-4. These transcription factors share highly-related COOH terminal leucine zipper dimerization and basic DNA binding but are highly divergent in their amino terminal domains. Although each of the ATF/CREB proteins bind CREs in their homodimeric form, in certain instances they also bind as heterodimers, both within the ATF/CREB family and with members of the AP-1 transcription factor family. It has recently been shown that protein kinase A-mediated CREB phosphorylation results in its binding to a 265-kDa nuclear protein designated CBP (CREB-binding protein), which represents a CREB co-activator. Phosphorylation of Ser-133 is key for CREB transcriptional activity.