Reference - Detail
| RRC ID | 47082 |
|---|---|
| Author | Wang X, Wang Z, Chen Y, Huang X, Hu Y, Zhang R, Ho MS, Xue L. |
| Title | FoxO mediates APP-induced AICD-dependent cell death. |
| Journal | Cell Death Dis |
| Abstract |
The amyloid precursor protein (APP) is a broadly expressed transmembrane protein that has a significant role in the pathogenesis of Alzheimer's disease (AD). APP can be cleaved at multiple sites to generate a series of fragments including the amyloid β (Aβ) peptides and APP intracellular domain (AICD). Although Aβ peptides have been proposed to be the main cause of AD pathogenesis, the role of AICD has been underappreciated. Here we report that APP induces AICD-dependent cell death in Drosophila neuronal and non-neuronal tissues. Our genetic screen identified the transcription factor forkhead box O (FoxO) as a crucial downstream mediator of APP-induced cell death and locomotion defect. In mammalian cells, AICD physically interacts with FoxO in the cytoplasm, translocates with FoxO into the nucleus upon oxidative stress, and promotes FoxO-induced transcription of pro-apoptotic gene Bim. These data demonstrate that APP modulates FoxO-mediated cell death through AICD, which acts as a transcriptional co-activator of FoxO. |
| Volume | 5(5) |
| Pages | e1233 |
| Published | 2014-5-15 |
| DOI | 10.1038/cddis.2014.196 |
| PII | cddis2014196 |
| PMID | 24832605 |
| PMC | PMC4047897 |
| MeSH | Amyloid beta-Protein Precursor / genetics Amyloid beta-Protein Precursor / metabolism* Animals Animals, Genetically Modified Apoptosis Regulatory Proteins / genetics Apoptosis Regulatory Proteins / metabolism Bcl-2-Like Protein 11 Cell Death Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / embryology Drosophila melanogaster / genetics Drosophila melanogaster / metabolism* Flight, Animal Forkhead Transcription Factors / genetics Forkhead Transcription Factors / metabolism* HEK293 Cells Humans Membrane Proteins / genetics Membrane Proteins / metabolism Protein Structure, Tertiary Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Signal Transduction Transfection Wings, Animal / embryology Wings, Animal / metabolism* Wings, Animal / pathology |
| IF | 6.304 |
| Times Cited | 33 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Drosophila | |