Abstract
The cyclic AMP response element-binding protein (CREB) is involved in the development and function of the nervous system. Here, we find that CREB decreases the protein level of Regulator of Calcineurin Activity 1 (RCAN1/DSCR1/MCIP1), which is overexpressed in the brain of Down Syndrome (DS) patients. Decrease of RCAN1 by CREB was blocked by proteasome inhibitors, indicating that this decrease is mediated by the ubiquitin-proteasome pathway. Furthermore, we found that the ability of CREB to activate the degradation of RCAN1 depends on its transcriptional activation. Consistently, CREB-enhanced the ubiquitination and turnover rate of RCAN1. Our results reveal a new regulatory role for CREB in DS pathology through the proteasomal degradation of RCAN1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cells, Cultured
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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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Cysteine Proteinase Inhibitors / pharmacology
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DNA-Binding Proteins
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Down Syndrome / enzymology
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism*
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Neurons / metabolism*
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Proteasome Endopeptidase Complex / metabolism*
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Proteasome Inhibitors
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Transcriptional Activation*
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Ubiquitination*
Substances
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CREB1 protein, human
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Cyclic AMP Response Element-Binding Protein
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Cysteine Proteinase Inhibitors
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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Muscle Proteins
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Proteasome Inhibitors
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RCAN1 protein, human
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Proteasome Endopeptidase Complex