title: Amyloid precursor protein binding protein-1 modulates cell cycle progression in fetal neural stem cells.
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 phosphorylation of threonine 668.
authors.affiliation: Department of Pharmacology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
authors.forename: Yuyoung
authors.initials: Y
authors.lastname: Joo
authors.forename: Sungji
authors.initials: S
authors.lastname: Ha
authors.forename: Bo-Hyun
authors.initials: BH
authors.lastname: Hong
authors.forename: Jeong a
authors.initials: Ja
authors.lastname: Kim
authors.forename: Keun-A
authors.initials: KA
authors.lastname: Chang
authors.forename: Hyunjeong
authors.initials: H
authors.lastname: Liew
authors.forename: Seonghan
authors.initials: S
authors.lastname: Kim
authors.forename: Woong
authors.initials: W
authors.lastname: Sun
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Hae
authors.initials: YH
authors.lastname: Chong
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D002453:Cell Cycle; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology*; D031541:Fluorescence Resonance Energy Transfer; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044764:Ubiquitin-Activating Enzymes
chemical_list: D016564:Amyloid beta-Protein Precursor; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D044764:Ubiquitin-Activating Enzymes; C491802:NAE protein, human