APP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation

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dc.contributor.authorShu, R.
dc.contributor.authorWong, W.
dc.contributor.authorMa, Q.H.
dc.contributor.authorYang, Z.Z.
dc.contributor.authorZhu, H.
dc.contributor.authorLiu, F.J.
dc.contributor.authorWang, P.
dc.contributor.authorMa, J.
dc.contributor.authorYan, S.
dc.contributor.authorPolo, J.M.
dc.contributor.authorBernard, C.C.A.
dc.contributor.authorStanton, L.W.
dc.contributor.authorDawe, G.S.
dc.contributor.authorXiao, Z.C.
dc.date.issued2015
dc.description.abstractAmyloid 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.
dc.description.statementofresponsibilityR Shu, W Wong, Q H Ma, Z Z Yang, H Zhu, F J Liu ... et al.
dc.identifier.citationCell Death and Disease, 2015; 6(2):1-12
dc.identifier.doi10.1038/cddis.2015.10
dc.identifier.issn2041-4889
dc.identifier.issn2041-4889
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/133508
dc.language.isoen
dc.publisherNature Publishing
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1053621
dc.rights© 2015 Macmillan Publishers Limited All rights reserved. Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International Licence. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons licence, users will need to obtain permission from the licence holder to reproduce the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0
dc.source.urihttps://doi.org/10.1038/cddis.2015.10
dc.subjectNeurons
dc.subjectCell Line
dc.subjectHumans
dc.subjectAmyloid beta-Protein Precursor
dc.subjectDNA-Binding Proteins
dc.subjectMicroRNAs
dc.subjectChromatin Immunoprecipitation
dc.subjectCell Differentiation
dc.subjectGene Expression Regulation
dc.subjectProtein Binding
dc.subject.meshNeurons
dc.subject.meshCell Line
dc.subject.meshHumans
dc.subject.meshAmyloid beta-Protein Precursor
dc.subject.meshDNA-Binding Proteins
dc.subject.meshMicroRNAs
dc.subject.meshChromatin Immunoprecipitation
dc.subject.meshCell Differentiation
dc.subject.meshGene Expression Regulation
dc.subject.meshProtein Binding
dc.titleAPP intracellular domain acts as a transcriptional regulator of miR-663 suppressing neuronal differentiation
dc.typeJournal article
pubs.publication-statusPublished

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