Title

DNA damage induces cdk2 protein levels and histone H2B phosphorylation in SH-SY5Y neuroblastoma cells

Document Type

Article

Abstract

DNA damage and activation of the cell cycle have been implicated in numerous neurodegenerative diseases, including Alzheimer disease, Parkinson's disease, and amyotrophic lateral sclerosis. To better understand the role of cell cycle proteins in DNA-damage induced neuronal cell death, we examined various cell cycle proteins during camptothecin-induced death of human neuroblastoma cells. We report a rapid induction of p53 and increased expression of p21, concurrent with reduced levels of many cell cycle proteins that regulate G1 to S phase cell cycle progression. However, we found increased levels of cdk2 and cyclin E, and formation of a cyclin E-cdk2-p21 protein complex. DNA damage failed to induce activation and progression of the cell cycle. Finally, camptothecin-induced neuronal cell death occurred concurrent with phosphorylation of histone H2B. Pretreatment of cells with cdk inhibitor olomoucine impeded cdk2-cyclin E accumulation, but not the induction of p53. Olomucine concurrently delayed histone H2B phosphorylation, caspase-3 activation and cell death. These findings suggest that DNA-damage of differentiated neuroblastoma cells induces a rapid p53-mediated inhibition of cell cycle progression and induction of cdk2-cyclin E, followed by caspase-3 activation, phosphorylation of histone and cell death. © 2005 - IOS Press and the authors. All rights reserved.

Publication Date

1-1-2005

Publication Title

Journal of Alzheimer's Disease

ISSN

13872877

Volume

8

Issue

1

First Page

7

Last Page

21

PubMed ID

16155345

Digital Object Identifier (DOI)

10.3233/JAD-2005-8102

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