Document Detail


Regulation of FE65 nuclear translocation and function by amyloid beta-protein precursor in osmotically stressed cells.
MedLine Citation:
PMID:  18468999     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
FE65, a neural adaptor protein, interacts with amyloid beta-protein precursor (APP) and is known to regulate amyloid beta generation from APP. FE65 also associates with nuclear proteins; however, its physiological function in the nucleus remains unclear. A fixed population of cytoplasmic FE65 is tethered to membranes by binding APP. This membrane-tethered FE65 is liberated from membranes by APP phosphorylation, which is facilitated by a stress-activated protein kinase in sorbitol-treated cells. Here we show that liberated FE65, which is distinct from "virgin" FE65 in the cytoplasm, translocates into the nucleus and accumulates in the nuclear matrix forming a patched structure. Targeting of FE65 into the nuclear matrix was suppressed by the APP intracellular domain fragment, which is generated by consecutive cleavages of APP. Thus, nuclear translocation of FE65 is under the regulation of APP. In the nucleus, FE65 induced gammaH2AX, which plays an important role in DNA repair as a cellular response by stress-damaged cells. These observations suggest that APP-regulated FE65 plays an important role in the early stress response of cells and that FE65 deregulated from APP induces apoptosis.
Authors:
Tadashi Nakaya; Tomoko Kawai; Toshiharu Suzuki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-09
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-06-30     Completed Date:  2008-08-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19119-31     Citation Subset:  IM    
Affiliation:
Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
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MeSH Terms
Descriptor/Qualifier:
Active Transport, Cell Nucleus / drug effects
Adenosine Triphosphate / metabolism*
Amyloid beta-Protein Precursor / genetics,  metabolism*
Animals
Apoptosis / drug effects
Cell Line, Tumor
Cytoplasm / genetics,  metabolism*
DNA Repair / drug effects
Histones / genetics,  metabolism
Humans
Mice
Nerve Tissue Proteins / genetics,  metabolism*
Nuclear Matrix / genetics,  metabolism*
Nuclear Proteins / genetics,  metabolism*
Osmotic Pressure / drug effects
Sorbitol / pharmacology
Sweetening Agents / pharmacology
Chemical
Reg. No./Substance:
0/APBB1 protein, human; 0/Amyloid beta-Protein Precursor; 0/Apbb1 protein, mouse; 0/H2AFX protein, human; 0/Histones; 0/Nerve Tissue Proteins; 0/Nuclear Proteins; 0/Sweetening Agents; 0/gamma-H2AX protein, mouse; 50-70-4/Sorbitol; 56-65-5/Adenosine Triphosphate

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