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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 33 time in
Web of Science
Cited 33 time in Scopus
- Authors
- Issue Date
- 2007
- Publisher
- Nature Publishing Group
- Citation
- Cell Death and Differentiation 2007; 14: 79-91
- Keywords
- Active Transport, Cell Nucleus ; Alzheimer Disease/*metabolism/pathology ; Amyloid beta-Protein Precursor/analysis/chemistry/genetics/*metabolism ; Animals ; Brain/*metabolism ; Brain Chemistry ; Cell Line ; Cell Nucleus/*metabolism ; DNA-Binding Proteins/*metabolism ; Fluorescence Resonance Energy Transfer ; Glycogen Synthase Kinase 3/analysis/*metabolism ; Green Fluorescent Proteins/genetics ; Humans ; Immunohistochemistry ; Matched-Pair Analysis ; Mice ; Nerve Tissue Proteins/analysis/genetics/metabolism ; Neurons/metabolism ; Nuclear Proteins/genetics/metabolism ; PC12 Cells ; Phosphorylation ; Point Mutation ; Protein Structure, Tertiary ; Rats ; Transcription Factors/*metabolism ; Transfection ; Up-Regulation ; tau 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
https://hdl.handle.net/10371/28184
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