title: Transcriptional regulation of CREB (cyclic AMP response element-binding protein) expression in CATH.a cells.
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.
authors.affiliation: Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Widnell
authors.forename: J S
authors.initials: JS
authors.lastname: Chen
authors.forename: P A
authors.initials: PA
authors.lastname: Iredale
authors.forename: W H
authors.initials: WH
authors.lastname: Walker
authors.forename: R S
authors.initials: RS
authors.lastname: Duman
authors.forename: J F
authors.initials: JF
authors.lastname: Habener
authors.forename: E J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000818:Animals; D001932:Brain Neoplasms; D002467:Cell Nucleus / Q000235:genetics; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000502:physiology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D005576:Colforsin