Mislocalization of CDK11/PITSLRE, a regulator of the G2/M phase of the cell cycle, in Alzheimer disease
| Autor: | Mark A. Smith, Hyoung Gon Lee, Biljana Spremo-Potparević, Ninoslav Djelic, Xiongwei Zhu, Lara M. Fahmy, Xinglong Wang, Zorana Milicevic, Bo Su, Vladan Bajic, Lada Živković, Sandra L. Siedlak, Avneet K. Singh, Wataru Kudo |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
G2 Phase Cell division Blotting Western Biochemistry Hippocampus Article Cell Line 03 medical and health sciences Amyloid beta-Protein Precursor Young Adult 0302 clinical medicine Cyclin-dependent kinase Alzheimer Disease Amyloid precursor protein Frozen Sections Humans Molecular Biology Mitosis 030304 developmental biology Aged Aged 80 and over Neurons 0303 health sciences biology Cell Biology Alzheimer's disease Cell cycle Middle Aged M17 cells Cyclin-Dependent Kinases Cell biology Transport protein Establishment of sister chromatid cohesion Protein Transport biology.protein Signal transduction Alzheimer disease APP 030217 neurology & neurosurgery Cell Division CDK11 |
| Zdroj: | Cellular and Molecular Biology Letters Cellular & Molecular Biology Letters |
| Popis: | Post-mitotic neurons are typically terminally differentiated and in a quiescent status. However, in Alzheimer disease (AD), many neurons display ectopic re-expression of cell cycle-related proteins. Cyclin-dependent kinase 11 (CDK11) mRNA produces a 110-kDa protein (CDK11p110) throughout the cell cycle, a 58-kDa protein (CDK11p58) that is specifically translated from an internal ribosome entry site and expressed only in the G2/M phase of the cell cycle, and a 46-kDa protein (CDK11p46) that is considered to be apoptosis specific. CDK11 is required for sister chromatid cohesion and the completion of mitosis. In this study, we found that the expression patterns of CDK11 vary such that cytoplasmic CDK11 is increased in AD cellular processes, compared to a pronounced nuclear expression pattern in most controls. We also investigated the effect of amyloid precursor protein (APP) on CDK11 expression in vitro by using M17 cells overexpressing wild-type APP and APP Swedish mutant phenotype and found increased CDK11 expression compared to empty vector. In addition, amyloid-β25–35 resulted in increased CDK11 in M17 cells. These data suggest that CDK11 may play a vital role in cell cycle re-entry in AD neurons in an APP-dependent manner, thus presenting an intriguing novel function of the APP signaling pathway in AD. |
| Databáze: | OpenAIRE |
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