Cyclic AMP-stimulated accumulation of the cAMP response element binding protein can occur without changes in gene...

The cAMP response element binding protein (CREB) is expressed at constitutively low levels in most cell types, and the CREB promoter possesses features that are typical of house-keeping genes. Since the CREB promoter also contains sequences which can mediate cAMP responsiveness in transfection experiments, it has been proposed that transcription of the CREB gene is controlled by positive autoregulation. In the present study, we show that cAMP does not regulate the level of CREB mRNA in any of the tissue-or cell-types that we examined, nor is expression regulated by other hormones which commonly affect gene expression. However, treatment of rat hepatoma cells with cAMP did result in accumulation of CREB protein. We conclude that the positive autoregulation of CREB expression which has been proposed is not ubiquitously operational, although CREB protein levels can be regulated in a cell-specific manner which does not involve transcriptional activation of the CREB gene.