Document Detail

Synergistic activation of neurotensin/neuromedin N gene expression by c-Jun and glucocorticoids: novel effects of Fos family proteins.
MedLine Citation:
PMID:  7476995     Owner:  NLM     Status:  MEDLINE    
The cis-regulatory region of the neurotensin/neuromedin N (NT/N) gene integrates diverse environmental signals in the neuroendocrine PC12 cell line, resulting in remarkable synergistic regulation. An AP-1 site appears to play a pivotal role in cooperative NT/N gene activation, as mutations in this site decrease responses to all inducer combinations by at least an order of magnitude. Here we report that c-Jun acts synergistically with glucocorticoids to activate the NT/N promoter, and that Fos family proteins have novel regulatory effects on this interaction. Cotransfection of individual pCMV-AP-1 expression plasmids revealed that c-Jun most potently activates the NT/N promoter and that costimulation with dexamethasone results in a further 6- to 12-fold increase in expression. Unlike its general inhibitory effects on glucocorticoid regulation in other systems, c-Fos potentiated activation by glucocorticoids when coexpressed with c-Jun, and Fos B had a similar, but more limited, positive effect. In contrast, Fra-1 reversed the direction of glucocorticoid regulation, and Fra-2 abolished synergism. AP-1, cAMP response element, and glucocorticoid response element motifs are required for full cooperative activation by either c-Jun or c-Jun/c-Fos and glucocorticoids. These results indicate that NT/N promoter activation involves synergistic interactions between specific AP-1 complexes and ligand-activated glucocorticoid receptor, and similar mechanisms may regulate NT/N gene expression in central neurons.
R J Harrison; G P McNeil; P R Dobner
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  9     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1995 Aug 
Date Detail:
Created Date:  1995-12-06     Completed Date:  1995-12-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  981-93     Citation Subset:  IM    
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655, USA.
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MeSH Terms
Base Sequence
Cyclic AMP Response Element-Binding Protein / metabolism
DNA Footprinting
DNA-Binding Proteins / physiology
Dexamethasone / pharmacology
Forskolin / pharmacology
Fos-Related Antigen-2
Gene Expression Regulation
Genes, jun
Molecular Sequence Data
Neurotensin / genetics*
Oligodeoxyribonucleotides / chemistry
PC12 Cells
Peptide Fragments / genetics*
Proto-Oncogene Proteins c-fos / physiology
Proto-Oncogene Proteins c-jun / physiology*
Receptors, Glucocorticoid / physiology
Regulatory Sequences, Nucleic Acid
Signal Transduction
Transcription Factor AP-1 / physiology*
Transcription Factors / physiology
Transcriptional Activation
Grant Support
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/DNA-Binding Proteins; 0/Fos-Related Antigen-2; 0/Fosl2 protein, rat; 0/Oligodeoxyribonucleotides; 0/Peptide Fragments; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Receptors, Glucocorticoid; 0/Transcription Factor AP-1; 0/Transcription Factors; 0/fos-related antigen 1; 102577-25-3/neuromedin N; 39379-15-2/Neurotensin; 50-02-2/Dexamethasone; 66428-89-5/Forskolin

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