DR5 and caspase-8 are dispensable in ER stress-induced apoptosis

Glab, JA; Doerflinger, M; Nedeva, C; Jose, I; Mbogo, GW; Paton, JC; Paton, AW; Kueh, AJ; Herold, MJ; Huang, DC; Segal, D; Brumatti, G; Puthalakath, H

Author(s): Glab, JA; Doerflinger, M; Nedeva, C; Jose, I; Mbogo, GW; Paton, JC; Paton, AW; Kueh, AJ; Herold, MJ; Huang, DC; Segal, D; Brumatti, G; Puthalakath, H;
Details: Publication Year 2017,Volume 24,Issue #5,Page 944-950
Journal Title: Cell Death and Differentiation
Publication Type: Journal Article
Abstract: The endoplasmic reticulum (ER) stress response constitutes cellular reactions triggered by a wide variety of stimuli that disturb folding of proteins, often leading to apoptosis. ER stress-induced apoptotic cell death is thought to be an important contributor to many human pathological conditions. The molecular mechanism of this apoptosis process has been highly controversial with both the receptor and the mitochondrial pathways being implicated. Using knockout mouse models and RNAi-mediated gene silencing in cell lines, our group and others had demonstrated the importance of the mitochondrial apoptotic pathway in ER stress-induced cell death, particularly the role of the pro-apoptotic BH3-only BCL-2 family members, BIM and PUMA. However, a recent report suggested a central role for the death receptor, DR5, activated in a ligand-independent manner, and the initiator caspase, caspase-8, in ER stress-induced cell death. This prompted us to re-visit our previous observations and attempt to reproduce the newly published findings. Here we report that the mitochondrial apoptotic pathway, activated by BH3-only proteins, is essential for ER stress-induced cell death and that, in contrast to the previous report, DR5 as well as caspase-8 are not required for this process.Cell Death and Differentiation advance online publication, 14 April 2017; doi:10.1038/cdd.2017.53.
Publisher: Springer Nature
Research Division(s): Infection And Immunity; Cancer And Haematology; Molecular Genetics Of Cancer; Cell Signalling And Cell Death
PubMed ID: 28409774
Publisher's Version: https://doi.org/10.1038/cdd.2017.53
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-05-02 03:01:26

Last Modified: 2018-07-09 03:48:07