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https://doi.org/10.1038/cddis.2015.10
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 microRNA 3648 microRNA 3687 microRNA 663 peptides and proteins unclassified drug amyloid precursor protein DNA binding protein microRNA MIRN663 microRNA, human protein binding Article chromatin immunoprecipitation controlled study gene expression human human cell microarray analysis nerve cell differentiation nervous system development neural stem cell priority journal protein domain transcription regulation cell differentiation cell line cytology gene expression regulation genetics metabolism nerve cell physiology Primates Amyloid beta-Protein Precursor Cell Differentiation Cell Line Chromatin Immunoprecipitation DNA-Binding Proteins Gene Expression Regulation Humans MicroRNAs Neurons 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. https://doi.org/10.1038/cddis.2015.10 | 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 | URI: | https://scholarbank.nus.edu.sg/handle/10635/175530 | ISSN: | 20414889 | DOI: | 10.1038/cddis.2015.10 |
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