CYCLIC AMP-STIMULATED ACCUMULATION OF THE CAMP RESPONSE ELEMENT-BINDING PROTEIN CAN OCCUR WITHOUT CHANGES IN GENE-EXPRESSION

The cAMP response element binding protein (CREB) is expressed at const itutively low levels in most cell types, and the CREB promoter possess es features that are typical of house-keeping genes. Since the CREB pr omoter also contains sequences which can mediate cAMP responsiveness i n transfection experiments, it has been proposed that transcription of the CREB gene is controlled by positive autoregulation. In the presen t 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 r egulated by other hormones which commonly affect gene expression. Howe ver, treatment of rat hepatoma cells with cAMP did result in accumulat ion of CREB protein. We conclude that the positive autoregulation of C REB expression which has been proposed is not ubiquitously operational , although CREB protein levels can be regulated in a cell-specific man ner which does not involve transcriptional activation of the CREB gene . (C) 1996 Academic Press, Inc.