Abstract
Cyclic AMP-regulated gene expression frequently involves a DNA element known as the cAMP-regulated enhancer (CRE). Many transcription factors bind to this element, including the protein CREB, which is activated as a result of phosphorylation by protein kinase A. This modification stimulates interaction with one or more of the general transcription factors or, alternatively, allows recruitment of a co-activator. Here we report that CREB phosphorylated by protein kinase A binds specifically to a nuclear protein of M(r) 265K which we term CBP (for CREB-binding protein). Fusion of a heterologous DNA-binding domain to the amino terminus of CBP enables the chimaeric protein to function as a protein kinase A-regulated transcriptional activator. We propose that CBP may participate in cAMP-regulated gene expression by interacting with the activated phosphorylated form of CREB.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites
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CREB-Binding Protein
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Cell Line
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Cloning, Molecular
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Cyclic AMP / physiology
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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DNA
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Gene Expression Regulation / physiology
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Genes, Reporter
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Humans
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Mice
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Molecular Sequence Data
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Nuclear Proteins / metabolism*
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Phosphorylation
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Protein Binding
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Thyroid Gland / metabolism
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Trans-Activators*
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Transcription Factors / metabolism*
Substances
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Cyclic AMP Response Element-Binding Protein
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Nuclear Proteins
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Recombinant Fusion Proteins
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Trans-Activators
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Transcription Factors
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DNA
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Cyclic AMP
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CREB-Binding Protein
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CREBBP protein, human
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Crebbp protein, mouse
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Cyclic AMP-Dependent Protein Kinases