TRANSCRIPTIONAL REGULATION OF CREB (CYCLIC-AMP RESPONSE ELEMENT-BINDING PROTEIN) EXPRESSION IN CATH.A CELLS

We have recently demonstrated that mRNA expression of cyclic AMP (cAMP ) response element-binding protein (CREB) is down-regulated in CATH.a cells (a neural-derived cell line) by activation of the cAMP pathway. We now demonstrate that this down-regulation can be accounted for by a decrease in the rate of CREB gene transcription. It was found that cy cloheximide, a protein synthesis inhibitor, prevented the forskolin-in duced decrease in CREB mRNA levels in CATH.a cells. Nuclear run-on ass ays demonstrated that forskolin decreased the rate of CREB transcripti on by close to 50%. Moreover, forskolin decreased chloramphenicol acet yltransferase (CAT) activity in CATH.a cells transiently transfected w ith a construct containing 1,240 bp of CREB promoter fused to a CAT re porter plasmid. Possible mechanisms by which activation of the cAMP pa thway leads to a decrease in CREB gene transcription are discussed.