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KMID : 0811720100140040229
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Korean Journal of Physiology & Pharmacology
2010 Volume.14 No. 4 p.229 ~ p.233
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Amyloid Precursor Protein Binding Protein-1 Is Up-regulated in Brains of Tg2576 Mice
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Yang Hyun-Jung
Joo Yu-Young
Hong Bo-Hyun
Ha Sung-Ji
Woo Ran-Sook
Lee Sang-Hyung
Suh Yoo-Hun
Kim Hye-Sun
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Abstract
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Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of amyloid precursor protein and serves as a bipartite activation enzyme for the ubiquitin-like protein, NEDD8. Previously, it has been reported that APP-BP1 rescues the cell cycle S-M checkpoint defect in Ts41 hamster cells, that this rescue is dependent on the interaction of APP-BP1 with hUba3. The exogenous expression of APP-BP1 in neurons has been reported to cause DNA synthesis and apoptosis via a signaling pathway that is dependent on APP-BP1 binding to APP. These results suggest that APP-BP1 overexpression contributes to neurodegeneration. In the present study, we explored whether APP-BP1 expression was altered in the brains of Tg2576 mice, which is an animal model of Alzheimer’s disease. APP-BP1 was found to be up-regulated in the hippocampus and cortex of 12 month-old Tg2576 mice compared to age-matched wild-type mice. In addition, APP-BP1 knockdown by siRNA treatment reduced cullin-1 neddylation in fetal neural stem cells, suggesting that APP-BP1 plays a role in cell cycle progression in the cells. Collectively, these results suggest that increased expression of APP-BP1, which has a role in cell cycle progression in neuronal cells, contributes to the pathogenesis of Alzheimer’s disease.
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KEYWORD
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Amyloid precursor protein binding protein-1, Amyloid precursor protein, Alzheimer’s disease, cell cycle, Tg2576 mice
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