Abstract
Families bearing mutations in the presenilin-1 (PSI) gene develop Alzheimer's disease (AD). However, the mechanism through which PS1 causes AD is unclear. The co-immunoprecipitation with PS1 in transfected COS-7 cells indicates that PSI directly interacts with endogenous beta-catenin, and the interaction requires residues 322450 of PSI and 445-676 of beta-catenin. Both proteins are co-localized in the endoplasmic reticulum. Over-expression of PS1 reduces the level of cytoplasmic beta-catenin, and inhibits beta-catenin-T cell factor-regulated transcription. These results indicate that PSI plays a role as inhibitor of the beta-catenin signal, which may be connected with the AD dysfunction.
MeSH terms
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Alzheimer Disease
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Animals
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Binding Sites
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COS Cells
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Cytoplasm / metabolism
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Cytoskeletal Proteins / chemistry
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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Endoplasmic Reticulum / chemistry
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Gene Expression
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Humans
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Immunosorbent Techniques
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mutagenesis, Site-Directed
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Neuroblastoma / chemistry
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Peptide Fragments / chemistry
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Presenilin-1
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Signal Transduction
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Structure-Activity Relationship
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Trans-Activators*
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Transfection
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Tumor Cells, Cultured
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beta Catenin
Substances
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CTNNB1 protein, human
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Cytoskeletal Proteins
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Membrane Proteins
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PSEN1 protein, human
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Peptide Fragments
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Presenilin-1
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Trans-Activators
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beta Catenin