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Amyloid precursor protein binding protein-1 modulates cell cycle progression in fetal neural stem cells

Title
Amyloid precursor protein binding protein-1 modulates cell cycle progression in fetal neural stem cells
Authors
Joo Y.Ha S.Hong B.-H.Kim J.A.Chang K.-A.Liew H.Kim S.Sun W.Kim J.-H.Chong Y.H.Suh Y.-H.Kim H.-S.
Ewha Authors
정영해
SCOPUS Author ID
정영해scopus
Issue Date
2010
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 5, no. 12
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Amyloid precursor protein binding protein-1 (APP-BP1) binds to the carboxyl terminus of the amyloid precursor protein (APP) and serves as the bipartite activation enzyme for the ubiquitin-like protein, NEDD8. In the present study, we explored the physiological role of APP-BP1 in the cell cycle progression of fetal neural stem cells. Our results show that cell cycle progression of the cells is arrested at the G1 phase by depletion of APP-BP1, which results in a marked decrease in the proliferation of the cells. This action of APP-BP1 is antagonistically regulated by the interaction with APP. Consistent with the evidence that APP-BP1 function is critical for cell cycle progression, the amount of APP-BP1 varies depending upon cell cycle phase, with culminating expression at S-phase. Furthermore, our FRET experiment revealed that phosphorylation of APP at threonine 668, known to occur during the G2/M phase, is required for the interaction between APP and APP-BP1. We also found a moderate ubiquitous level of APP-BP1 mRNA in developing embryonic and early postnatal brains; however, APP-BP1 expression is reduced by P12, and only low levels of APP-BP1 were found in the adult brain. In the cerebral cortex of E16 rats, substantial expression of both APP-BP1 and APP mRNAs was observed in the ventricular zone. Collectively, these results indicate that APP-BP1 plays an important role in the cell cycle progression of fetal neural stem cells, through the interaction with APP, which is fostered by phopshorylation of threonine 668. © 2010 Joo et al.
DOI
10.1371/journal.pone.0014203
Appears in Collections:
의학전문대학원 > 의학과 > Journal papers
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