Document Detail

Regulation of alpha-fetoprotein gene expression by antagonism between AP-1 and the glucocorticoid receptor at their overlapping binding site.
MedLine Citation:
PMID:  1708774     Owner:  NLM     Status:  MEDLINE    
We show here that the alpha-fetoprotein gene (AFP) promoter can be regulated by AP-1 activity using transient transfection assays. AFP promoter activity induced by c-jun/c-fos can be repressed by cotransfected glucocorticoid receptor. The DNA sequence conferring AP-1 activity was located in the proximal promoter region. Gel retardation assays using the AFP proximal promoter identified an AP-1-like sequence which can bind to bacterially expressed c-jun protein. This AP-1-like element, when cloned into the tk promoter, responds to the AP-1 activity of c-jun/c-fos products in both CV-1 and F-9 cells. The element overlaps with a consensus glucocorticoid-responsive element which was shown to confer negative modulation of AFP promoter activity. A 23-base pair DNA element containing the overlapping glucocorticoid-responsive element and AP-1 sites can be positively regulated by glucocorticoid receptor in the absence of c-jun/c-fos products. When plasmids expressing glucocorticoid receptor, c-jun and c-fos are cotransfected together, they repress each other. Thus, these data demonstrate that negative regulation of the AFP gene by glucocorticoid may be due to the interference of AP-1 activity by glucocorticoid receptor either by direct competition for DNA binding or via protein-protein interaction. They provide another example of transcriptional regulation of developing-associated genes between two major signal transduction pathways in response to extracellular stimuli. This supports the model that expression of alpha-fetoprotein is regulated during development by the effect on transcription of antagonism between glucocorticoid receptor and fos/jun.
X K Zhang; J M Dong; J F Chiu
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  266     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1991 May 
Date Detail:
Created Date:  1991-06-05     Completed Date:  1991-06-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  8248-54     Citation Subset:  IM    
Department of Biochemistry, University of Vermont, College of Medicine, Burlington 05405.
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MeSH Terms
Base Sequence
Binding Sites
Cloning, Molecular
DNA-Binding Proteins / genetics,  metabolism*
Dexamethasone / pharmacology
Gene Expression Regulation*
Molecular Sequence Data
Promoter Regions, Genetic
Proto-Oncogene Proteins / genetics,  metabolism
Proto-Oncogene Proteins c-fos
Proto-Oncogene Proteins c-jun
Receptors, Glucocorticoid / metabolism*
Transcription Factors / genetics,  metabolism*
Tumor Cells, Cultured
alpha-Fetoproteins / genetics*
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; 0/Receptors, Glucocorticoid; 0/Transcription Factors; 0/alpha-Fetoproteins; 50-02-2/Dexamethasone

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