Abstract
Recruitment of the coactivator, CREB binding protein (CBP), by signal-regulated transcription factors, such as CREB [adenosine 3', 5'-monophosphate (cAMP) response element binding protein], is critical for stimulation of gene expression. The mouse pituitary cell line AtT20 was used to show that the CBP recruitment step (CREB phosphorylation on serine-133) can be uncoupled from CREB/CBP-activated transcription. CBP was found to contain a signal-regulated transcriptional activation domain that is controlled by nuclear calcium and calcium/calmodulin-dependent (CaM) protein kinase IV and by cAMP. Cytoplasmic calcium signals that stimulate the Ras mitogen-activated protein kinase signaling cascade or expression of the activated form of Ras provided the CBP recruitment signal but did not increase CBP activity and failed to activate CREB- and CBP-mediated transcription. These results identify CBP as a signal-regulated transcriptional coactivator and define a regulatory role for nuclear calcium and cAMP in CBP-dependent gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CREB-Binding Protein
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Calcium / metabolism*
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Calcium Channels / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cell Line
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Cell Nucleus / metabolism*
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Cyclic AMP / metabolism
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Cyclic AMP Response Element-Binding Protein / metabolism
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Cytoplasm / metabolism
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Genes, Reporter
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Mice
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Models, Genetic
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Nuclear Proteins / metabolism*
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Phosphorylation
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Phosphoserine / metabolism
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Trans-Activators / metabolism*
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Transcription, Genetic
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Transcriptional Activation*
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ras Proteins / metabolism
Substances
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Calcium Channels
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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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Phosphoserine
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Cyclic AMP
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CREB-Binding Protein
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Crebbp protein, mouse
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases
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Camk4 protein, mouse
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ras Proteins
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Calcium