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Intracellular domains of amyloid precursor-like protein 2 interact with CP2 transcription factor in the nucleus and induce glycogen synthase kinase-3beta expression

Cited 32 time in Web of Science Cited 30 time in Scopus
Authors
Xu, Y.; Kim, H. S.; Joo, Y.; Choi, Y.; Chang, K. A.; Park, C. H.; Shin, K. Y.; Kim, S.; Cheon, Y. H.; Baik, T. K.; Kim, J. H.; Suh, Y. H.
Issue Date
2007
Publisher
Nature Publishing Group
Citation
Cell Death and Differentiation 2007; 14: 79-91
Keywords
Active Transport, Cell NucleusAlzheimer Disease/*metabolism/pathologyAmyloid beta-Protein Precursor/analysis/chemistry/genetics/*metabolismAnimalsBrain/*metabolismBrain ChemistryCell LineCell Nucleus/*metabolismDNA-Binding Proteins/*metabolismFluorescence Resonance Energy TransferGlycogen Synthase Kinase 3/analysis/*metabolismGreen Fluorescent Proteins/geneticsHumansImmunohistochemistryMatched-Pair AnalysisMiceNerve Tissue Proteins/analysis/genetics/metabolismNeurons/metabolismNuclear Proteins/genetics/metabolismPC12 CellsPhosphorylationPoint MutationProtein Structure, TertiaryRatsTranscription Factors/*metabolismTransfectionUp-Regulationtau Proteins/metabolism
Abstract
Amyloid precursor protein (APP) is a member of a gene family that includes two APP-like proteins, APLP1 and 2. Recently, it has been reported that APLP1 and 2 undergo presenilin-dependent gamma-secretase cleavage, as does APP, resulting in the release of an approximately 6 kDa intracellular C-terminal domain (ICD), which can translocate into the nucleus. In this study, we demonstrate that the APLP2-ICDs interact with CP2/LSF/LBP1 (CP2) transcription factor in the nucleus and induce the expression of glycogen synthase kinase 3beta (GSK-3beta), which has broad-ranged substrates such as tau- and beta-catenin. The significance of this finding is substantiated by the in vivo evidence of the increase in the immunoreactivities for the nuclear C-terminal fragments of APLP2, and for GSK-3beta in the AD patients' brain. Taken together, these results suggest that APLP2-ICDs contribute to the AD pathogenesis, by inducing GSK-3beta expression through the interaction with CP2 transcription factor in the nucleus.
ISSN
1350-9047 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16645641

http://hdl.handle.net/10371/28184
DOI
https://doi.org/10.1038/sj.cdd.4401928
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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