Abstract
Mutations in the presenilin 1 (PS1) gene have been associated to familial Alzheimer disease although the exact pathogenic mechanism is unclear. We report that stable overexpression of wild type PS1 led to a decrease in cyclin-dependent kinase 4 (CDK 4) activity and retinoblastoma tumor suppressor protein (pRb) phosphorylation that correlated with decreased levels of beta-catenin and cyclin D1. PS1 mutant D385A also precipitated a similar effect suggesting that gamma-secretase cleavage is not essential for PS1-mediated CDK 4 inhibition. We postulate that PS1 overexpression may balance the hyperphosphorylation of pRb associated with death of post mitotic neurons after injury.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism
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Animals
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CHO Cells
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Cell Culture Techniques
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Cricetinae
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Cyclin D1 / metabolism*
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases / metabolism*
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Cytoskeletal Proteins / metabolism*
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Immunoblotting
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Membrane Proteins / metabolism*
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Neurodegenerative Diseases / metabolism
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Phosphorylation / drug effects
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Presenilin-1
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Protein Kinases / metabolism*
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Proto-Oncogene Proteins*
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Retinoblastoma Protein / metabolism*
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Trans-Activators / metabolism*
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Transfection
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Up-Regulation / drug effects
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beta Catenin
Substances
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Cytoskeletal Proteins
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Membrane Proteins
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Presenilin-1
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Proto-Oncogene Proteins
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Retinoblastoma Protein
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Trans-Activators
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beta Catenin
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Cyclin D1
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Protein Kinases
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinases