Abstract
Calcineurin (CN) is an important regulator of developmental processes and in adults controls the immune response through its regulation of nuclear factor of activated T cells (NFAT). The physical interaction between CN and NFATs is an essential step in the activation of NFAT-dependent genes by calcium signals. Using deletional and substitutional analyses, we have identified a 13-amino acid region within CN that is essential for the interaction with NFAT and with two other CN-binding proteins, AKAP79 and Cabin-1. The interaction of CN with these proteins is selectively disrupted by substitution of specific amino acid residues within this region, indicating that NFAT and other CN-interacting proteins bind differentially to CN. This selectivity suggests that the region identified in CN could be a potential molecular target for immunosuppressive and other therapeutic interventions in diseases involving the CN/NFAT pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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A Kinase Anchor Proteins
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Active Transport, Cell Nucleus
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Adaptor Proteins, Signal Transducing / chemistry
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Calcineurin / chemistry*
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Calcium / metabolism
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Catalytic Domain
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Cell Line
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Cell Nucleus / metabolism
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DNA Mutational Analysis
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DNA-Binding Proteins / chemistry*
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Gene Deletion
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Glutathione Transferase / metabolism
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HeLa Cells
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Humans
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Immunosuppressive Agents / chemistry
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Microscopy, Fluorescence
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Models, Biological
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NFATC Transcription Factors
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Nuclear Proteins / chemistry*
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Oligopeptides / chemistry
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Plasmids / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / metabolism
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Transcription Factors / chemistry*
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Transfection
Substances
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A Kinase Anchor Proteins
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AKAP5 protein, human
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Adaptor Proteins, Signal Transducing
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DNA-Binding Proteins
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Immunosuppressive Agents
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NFATC Transcription Factors
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Nuclear Proteins
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Oligopeptides
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Recombinant Fusion Proteins
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Transcription Factors
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cabin-1
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Glutathione Transferase
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Calcineurin
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Calcium