1. Intracellular domains of amyloid precursor-like protein 2 interact with CP2 transcription factor in the nucleus and induce glycogen synthase kinase-3β expression
- Author
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Ki Young Shin, Yoori Choi, Jae Ho Kim, Cheol-Hyoung Park, Yoo-Hun Suh, Yuyoung Joo, Xu Y, Soyoung Kim, Keun-A Chang, Hyun-Chul Kim, Cheon Yh, and Baik Tk
- Subjects
Matched-Pair Analysis ,Green Fluorescent Proteins ,Active Transport, Cell Nucleus ,Nerve Tissue Proteins ,tau Proteins ,Transfection ,PC12 Cells ,DNA-binding protein ,Cell Line ,Amyloid beta-Protein Precursor ,Glycogen Synthase Kinase 3 ,Mice ,Alzheimer Disease ,GSK-3 ,mental disorders ,Fluorescence Resonance Energy Transfer ,medicine ,Amyloid precursor protein ,Animals ,Humans ,Point Mutation ,APLP1 ,Phosphorylation ,Nuclear protein ,Molecular Biology ,Transcription factor ,GSK3B ,Brain Chemistry ,Cell Nucleus ,Neurons ,Glycogen Synthase Kinase 3 beta ,biology ,Brain ,Nuclear Proteins ,Cell Biology ,Immunohistochemistry ,Molecular biology ,Protein Structure, Tertiary ,Rats ,Up-Regulation ,DNA-Binding Proteins ,Cell nucleus ,medicine.anatomical_structure ,biology.protein ,Transcription Factors - 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.
- Published
- 2006