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 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.
Widnell
K L
KL
Laboratory of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA.
Chen
J S
JS
Iredale
P A
PA
Walker
W H
WH
Duman
R S
RS
Habener
J F
JF
Nestler
E J
EJ
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
D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D005576:Colforsin