Transcriptional Regulation of CREB (Cyclic AMP Response Element‐Binding Protein) Expression in CATH.a Cells

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Abstract
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 cycloheximide, a protein synthesis inhibitor, prevented the forskolin‐induced decrease in CREB mRNA levels in CATH.a cells. Nuclear run‐on assays demonstrated that forskolin decreased the rate of CREB transcription by close to 50%. Moreover, forskolin decreased chloramphenicol acetyltransferase (CAT) activity in CATH.a cells transiently transfected with a construct containing 1,240 bp of CREB promoter fused to a CAT reporter plasmid. Possible mechanisms by which activation of the cAMP pathway leads to a decrease in CREB gene transcription are discussed.

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