論文 - 詳細
| RRC ID | 31962 |
|---|---|
| 著者 | Demay Y, Perochon J, Szuplewski S, Mignotte B, Gaumer S. |
| タイトル | The PERK pathway independently triggers apoptosis and a Rac1/Slpr/JNK/Dilp8 signaling favoring tissue homeostasis in a chronic ER stress Drosophila model. |
| ジャーナル | Cell Death Dis |
| Abstract |
The endoplasmic reticulum (ER) has a major role in protein folding. The accumulation of unfolded proteins in the ER induces a stress, which can be resolved by the unfolded protein response (UPR). Chronicity of ER stress leads to UPR-induced apoptosis and in turn to an unbalance of tissue homeostasis. Although ER stress-dependent apoptosis is observed in a great number of devastating human diseases, how cells activate apoptosis and promote tissue homeostasis after chronic ER stress remains poorly understood. Here, using the Drosophila wing imaginal disc as a model system, we validated that Presenilin overexpression induces chronic ER stress in vivo. We observed, in this novel model of chronic ER-stress, a PERK/ATF4-dependent apoptosis requiring downregulation of the antiapoptotic diap1 gene. PERK/ATF4 also activated the JNK pathway through Rac1 and Slpr activation in apoptotic cells, leading to the expression of Dilp8. This insulin-like peptide caused a developmental delay, which partially allowed the replacement of apoptotic cells. Thanks to a novel chronic ER stress model, these results establish a new pathway that both participates in tissue homeostasis and triggers apoptosis through an original regulation. |
| 巻・号 | 5(10) |
| ページ | e1452 |
| 公開日 | 2014-10-9 |
| DOI | 10.1038/cddis.2014.403 |
| PII | cddis2014403 |
| PMID | 25299777 |
| PMC | PMC4649510 |
| MeSH | Animals Apoptosis* Drosophila / cytology Drosophila / genetics Drosophila / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Endoplasmic Reticulum Stress* Humans Inhibitor of Apoptosis Proteins / genetics Inhibitor of Apoptosis Proteins / metabolism* Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* MAP Kinase Kinase 4 / genetics MAP Kinase Kinase 4 / metabolism* MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism* Models, Animal Presenilins / genetics Presenilins / metabolism Signal Transduction Unfolded Protein Response eIF-2 Kinase / genetics eIF-2 Kinase / metabolism* rac GTP-Binding Proteins / genetics rac GTP-Binding Proteins / metabolism* |
| IF | 6.304 |
| 引用数 | 21 |
| WOS 分野 | CELL BIOLOGY |
| リソース情報 | |
| ショウジョウバエ | 4353R-2 |