Abstract
We present evidence that the glucocorticoid receptor (GR) and transcription factor Jun/AP-1 can reciprocally repress one another's transcriptional activation by a novel mechanism that is independent of DNA binding. Overexpression of c-Jun prevents the glucocorticoid-induced activation of genes carrying a functional glucocorticoid response element (GRE). Conversely, GR is able to repress AP-1-mediated transcriptional activation. Mutant analysis reveals that the ligand binding and DNA binding domains of GR and the region including the leucine zipper of c-Jun are required for repression. Gel retardation analysis demonstrates that bacterially expressed c-Jun disrupts GR-GRE complexes. These data indicate that members of two distinct classes of transcription factors can oppose one another's activity through a mechanism likely involving protein-protein interactions.
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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Chromosome Deletion
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Dexamethasone / pharmacology*
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HeLa Cells / metabolism
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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 / physiology
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Proto-Oncogene Proteins c-jun
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Receptors, Glucocorticoid / genetics
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Receptors, Glucocorticoid / physiology*
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Repressor Proteins / physiology
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / genetics
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Transcription Factors / physiology*
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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 c-jun
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Receptors, Glucocorticoid
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Repressor Proteins
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Transcription Factors
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Dexamethasone
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Protein-Tyrosine Kinases
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Microbial Collagenase