501. Presenilin 1 overexpressions in Chinese hamster ovary (CHO) cells decreases the phosphorylation of retinoblastoma protein: relevance for neurodegeneration.
- Author
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Prat MI, Adamo AM, González SA, Affranchino JL, Ikeda M, Matsubara E, Shoji M, Smith MA, Castaño EM, and Morelli L
- Subjects
- Alzheimer Disease metabolism, Animals, CHO Cells, Cell Culture Techniques, Cricetinae, Cyclin-Dependent Kinase 4, Immunoblotting, Neurodegenerative Diseases metabolism, Phosphorylation drug effects, Presenilin-1, Transfection, Up-Regulation drug effects, beta Catenin, Cyclin D1 metabolism, Cyclin-Dependent Kinases metabolism, Cytoskeletal Proteins metabolism, Membrane Proteins metabolism, Protein Kinases metabolism, Proto-Oncogene Proteins, Retinoblastoma Protein metabolism, Trans-Activators metabolism
- 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.
- Published
- 2002
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