Abstract
Nuclear receptors regulate gene expression by direct activation of target genes and inhibition of AP-1. Here we report that, unexpectedly, activation by nuclear receptors requires the actions of CREB-binding protein (CBP) and that inhibition of AP-1 activity is the apparent result of competition for limiting amounts of CBP/p300 in cells. Utilizing distinct domains, CBP directly interacts with the ligand-binding domain of multiple nuclear receptors and with the p160 nuclear receptor coactivators, which upon cloning have proven to be variants of the SRC-1 protein. Because CBP represents a common factor, required in addition to distinct coactivators for function of nuclear receptors, CREB, and AP-1, we suggest that CBP/p300 serves as an integrator of multiple signal transduction pathways within the nucleus.
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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Base Sequence
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Binding Sites / genetics
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Binding, Competitive / genetics
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CREB-Binding Protein
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Cloning, Molecular
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Conserved Sequence
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DNA, Complementary / genetics
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Fibroblasts / physiology
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Gene Expression Regulation / genetics
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Histone Acetyltransferases
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Ligands
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Molecular Sequence Data
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Molecular Weight
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nuclear Proteins / pharmacology*
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Nuclear Receptor Coactivator 1
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Rats
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Receptors, Cytoplasmic and Nuclear / genetics*
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Receptors, Cytoplasmic and Nuclear / metabolism
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Sequence Homology, Amino Acid
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Trans-Activators*
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Transcription Factor AP-1 / antagonists & inhibitors*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / pharmacology*
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Transcriptional Activation / drug effects*
Substances
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DNA, Complementary
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Ligands
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Nuclear Proteins
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Receptors, Cytoplasmic and Nuclear
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Trans-Activators
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Transcription Factor AP-1
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Transcription Factors
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CREB-Binding Protein
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Crebbp protein, rat
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Histone Acetyltransferases
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Nuclear Receptor Coactivator 1