Abstract
Calcineurin phosphatase activity regulates the nuclear localization of the nuclear factor of activated T cells (NFAT) family of transcription factors during immune challenge. Calcineurin inhibitors, such as the cyclosporin A-cyclophilin A and FK506-FKBP12 complexes, regulate this enzymatic activity noncompetitively by binding at a site distinct from the enzyme active site. A family of endogenous protein inhibitors of calcineurin was recently identified and shown to block calcineurin-mediated NFAT nuclear localization and transcriptional activation. One such inhibitor, Down Syndrome Critical Region 1 (DSCR1), functions in T cell activation, cardiac hypertrophy, and angiogenesis. We have identified a small region of DSCR1 that is a potent inhibitor of calcineurin activity in vitro and in vivo.
Publication types
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Research Support, N.I.H., Extramural
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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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Active Transport, Cell Nucleus / drug effects
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Aniline Compounds / metabolism
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Animals
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Binding Sites
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Calcineurin / metabolism
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Calcineurin Inhibitors*
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Cell Line
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Cricetinae
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DNA-Binding Proteins / metabolism
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Exons
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Humans
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Intracellular Signaling Peptides and Proteins
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Kinetics
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Muscle Proteins / chemistry
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Muscle Proteins / pharmacology*
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NFATC Transcription Factors
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Nuclear Proteins / metabolism
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Organophosphorus Compounds / metabolism
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / pharmacology*
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Protein Binding
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Protein Interaction Mapping
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Protein Structure, Secondary
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Transcription Factors / metabolism
Substances
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Aniline Compounds
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Calcineurin 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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NFATC Transcription Factors
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Nuclear Proteins
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Organophosphorus Compounds
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Peptide Fragments
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RCAN1 protein, human
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Transcription Factors
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4-aminophenylphosphate
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Calcineurin