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Title: APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation
Authors: Shu, R
Wong, W
Ma, Q.H
Yang, Z.Z
Zhu, H
Liu, F.J
Wang, P
Ma, J
Yan, S
Polo, J.M
Bernard, C.C.A
Stanton, L.W 
Dawe, G.S 
Xiao, Z.C
Keywords: amyloid precursor protein
cyclin dependent kinase 6
FBXL18 protein
microRNA 3648
microRNA 3687
microRNA 663
peptides and proteins
unclassified drug
amyloid precursor protein
DNA binding protein
MIRN663 microRNA, human
protein binding
chromatin immunoprecipitation
controlled study
gene expression
human cell
microarray analysis
nerve cell differentiation
nervous system development
neural stem cell
priority journal
protein domain
transcription regulation
cell differentiation
cell line
gene expression regulation
nerve cell
Amyloid beta-Protein Precursor
Cell Differentiation
Cell Line
Chromatin Immunoprecipitation
DNA-Binding Proteins
Gene Expression Regulation
Protein Binding
Issue Date: 2015
Publisher: Nature Publishing Group
Citation: Shu, R, Wong, W, Ma, Q.H, Yang, Z.Z, Zhu, H, Liu, F.J, Wang, P, Ma, J, Yan, S, Polo, J.M, Bernard, C.C.A, Stanton, L.W, Dawe, G.S, Xiao, Z.C (2015). APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation. Cell Death and Disease 6 (2) : e1651. ScholarBank@NUS Repository.
Abstract: Amyloid precursor protein (APP) is best known for its involvement in the pathogenesis of Alzheimer's disease. We have previously demonstrated that APP intracellular domain (AICD) regulates neurogenesis; however, the mechanisms underlying AICD-mediated regulation of neuronal differentiation are not yet fully characterized. Using genome-wide chromatin immunoprecipitation approaches, we found that AICD is specifically recruited to the regulatory regions of several microRNA genes, and acts as a transcriptional regulator for miR-663, miR-3648 and miR-3687 in human neural stem cells. Functional assays show that AICD negatively modulates neuronal differentiation through miR-663, a primate-specific microRNA. Microarray data further demonstrate that miR-663 suppresses the expression of multiple genes implicated in neurogenesis, including FBXL18 and CDK6. Our results indicate that AICD has a novel role in suppression of neuronal differentiation via transcriptional regulation of miR-663 in human neural stem cells. © 2015 Macmillan Publishers Limited. All rights reserved.
Source Title: Cell Death and Disease
ISSN: 20414889
DOI: 10.1038/cddis.2015.10
Appears in Collections:Staff Publications

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