Presenilin 1 overexpressions in Chinese hamster ovary (CHO) cells decreases the phosphorylation of retinoblastoma protein: relevance for neurodegeneration.
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.
Prat
María I
MI
Instituto de Química y Fisicoquímica Biológicas (IQUIFIB) and Cátedra de Química Biológica Patológica, Departamento de Química Biológica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires-CONICET, Junin 956 (1113), Buenos Aires, Argentina.
Adamo
Ana M
AM
González
Silvia A
SA
Affranchino
José L
JL
Ikeda
Masaki
M
Matsubara
Etsuro
E
Shoji
Mikio
M
Smith
Mark A
MA
Castaño
Eduardo M
EM
Morelli
Laura
L
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D018929:Cell Culture Techniques; D006224:Cricetinae; D019938:Cyclin D1 / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015151:Immunoblotting; D008565:Membrane Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D053764:Presenilin-1; D011494:Protein Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D051176:beta Catenin
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D053764:Presenilin-1; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; D011494:Protein Kinases; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases