CHARACTERIZATION OF A BIPARTITE ACTIVATOR DOMAIN IN TRANSCRIPTION FACTOR CREB

In this paper, we characterize a trans-activating region in CREB, termed α, that interacts cooperatively with the kinase A phosphorylation motif to stimulate transcription. The α region appears to be encoded by an alternate axon that is deleted in a CREB-related cDNA named ΔCREB. Both proteins are expressed in eukaryotic cells, although the activity of CREB is 10-fold higher than that of ΔCREB. Circular dichroism data on a synthetic "α peptide" combined with results from in vitro mutagenesis experiments support the hypothesis that the a region contains an amphipathic α helix whose structure is critical to CREB activity. We propose that phosphorylation by kinase A may stimulate CREB activity in part by modulating the structure of α and thus may stimulate its ability to interact with other proteins in the polymerase 11 complex. © 1990.