Demay, Y., Perochon, J. , Szuplewski, S., Mignotte, B. and Gaumer, S. (2014) The PERK pathway independently triggers apoptosis and a Rac1/Slpr/JNK/Dilp8 signaling favoring tissue homeostasis in a chronic ER stress Drosophila model. Cell Death and Disease, 5, e1452. (doi: 10.1038/cddis.2014.403) (PMID:25299777) (PMCID:PMC4649510)
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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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Perochon, Miss Jessica |
Authors: | Demay, Y., Perochon, J., Szuplewski, S., Mignotte, B., and Gaumer, S. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Cell Death and Disease |
Publisher: | Nature Publishing Group |
ISSN: | 2041-4889 |
ISSN (Online): | 2041-4889 |
Copyright Holders: | Copyright © 2014 Macmillan Publishers Limited |
First Published: | First published in Cell Death and Disease 5: e1452 |
Publisher Policy: | Reproduced under a Creative Commons License |
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