S-Space College of Medicine/School of Medicine (의과대학/대학원) Pharmacology (약리학전공) Journal Papers (저널논문_약리학전공)
Intracellular domains of amyloid precursor-like protein 2 interact with CP2 transcription factor in the nucleus and induce glycogen synthase kinase-3beta expression
- 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
- Nature Publishing Group
- Cell Death and Differentiation 2007; 14: 79-91
- 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
- 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.
- 1350-9047 (Print)
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