Abstract
Glucocorticoids are potent inhibitors of collagenase induction by phorbol esters and inflammatory mediators. The target for this negative effect is the AP-1 site within the collagenase promoter, which also mediates its induction. Negative regulation is due to repression of AP-1 activity by the glucocorticoid receptor (GCR). While the GCR is a potent inhibitor of AP-1 activity (Jun/Fos), both c-Jun and c-Fos are potent repressors of GCR activity. In vitro experiments using purified GCR and c-Jun proteins suggest that mutual repression is due to direct interaction between the two. Direct interaction between GCR and either c-Jun or c-Fos is demonstrated by cross-linking and coimmunoprecipitation. These findings reveal a cross talk between two major signal transduction systems used to control gene transcription in response to extracellular stimuli, and a novel mechanism for transcriptional repression.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Dexamethasone / pharmacology*
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Gene Expression Regulation, Enzymologic
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HeLa Cells / drug effects
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HeLa Cells / enzymology
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Humans
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Microbial Collagenase / biosynthesis
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Microbial Collagenase / genetics*
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Plasmids
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Protein-Tyrosine Kinases / genetics
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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Proto-Oncogenes*
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Receptors, Glucocorticoid / physiology*
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription, Genetic* / drug effects
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Transfection
Substances
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DNA-Binding Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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Receptors, Glucocorticoid
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Transcription Factors
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Dexamethasone
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Protein-Tyrosine Kinases
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Microbial Collagenase