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Transcriptional Regulation of CREB (Cyclic AMP Response Element‐Binding Protein) Expression in CATH.a Cells
Author(s) -
Widnell Katherine L.,
Chen JingShan,
Iredale Philip A.,
Walker William H.,
Duman Ronald S.,
Habener Joel F.,
Nestler Eric J.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66041770.x
Subject(s) - creb , forskolin , cyclic amp response element binding protein , cycloheximide , microbiology and biotechnology , transcription (linguistics) , activator (genetics) , transfection , chloramphenicol acetyltransferase , response element , gene expression , transcription factor , biology , reporter gene , creb1 , chemistry , gene , protein biosynthesis , cell culture , promoter , biochemistry , genetics , linguistics , philosophy
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.