| 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
|
| Resource |
| Drosophila |
|
