ACTIVATING TRANSCRIPTION FACTOR-I IS A SPECIFIC ANTAGONIST OF THE CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE (CAMP) RESPONSE ELEMENT-BINDING PROTEIN-1-MEDIATED RESPONSE TO CAMP

We have investigated the molecular basis of the variability of the som atostatin cAMP response element (CRE) function in different cell lines . All cells tested contain detectable levels of the CRE-binding protei n CREB-1, which mediates transactivation in response to the cAMP-depen dent protein kinase (protein kinase-A), in forms that can bind to a so matostatin CRE. Although both responsive and nonresponsive cells conta in CREB-1 in heterodimers with activating transcription factor-1 (ATF- 1), only cells that allow a cAMP response have a significant proportio n of CREB-1 in a homodimeric form. Transfection experiments demonstrat e that ATF-1 is capable of antagonizing CREB-1-dependent activation, s uggesting that the ability of CREB-1 to mediate a cAMP response is dow n-regulated by heterodimer formation with ATF-1.