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Divergent effects of PERK and IRE1 signaling on cell viability.
- Source :
-
PloS one [PLoS One] 2009; Vol. 4 (1), pp. e4170. Date of Electronic Publication: 2009 Jan 12. - Publication Year :
- 2009
-
Abstract
- Protein misfolding in the endoplasmic reticulum (ER) activates a set of intracellular signaling pathways, collectively termed the Unfolded Protein Response (UPR). UPR signaling promotes cell survival by reducing misfolded protein levels. If homeostasis cannot be restored, UPR signaling promotes cell death. The molecular basis for the switch between prosurvival and proapoptotic UPR function is poorly understood. The ER-resident proteins, PERK and IRE1, control two key UPR signaling pathways. Protein misfolding concomitantly activates PERK and IRE1 and has clouded insight into their contributions toward life or death cell fates. Here, we employed chemical-genetic strategies to activate individually PERK or IRE1 uncoupled from protein misfolding. We found that sustained PERK signaling impaired cell proliferation and promoted apoptosis. By contrast, equivalent durations of IRE1 signaling enhanced cell proliferation without promoting cell death. These results demonstrate that extended PERK and IRE1 signaling have opposite effects on cell viability. Differential activation of PERK and IRE1 may determine life or death decisions after ER protein misfolding.
- Subjects :
- Cell Line
Humans
Poly(ADP-ribose) Polymerases metabolism
Protein Folding
Signal Transduction
Apoptosis physiology
Cell Survival physiology
Endoplasmic Reticulum enzymology
Endoribonucleases metabolism
Membrane Proteins metabolism
Protein Serine-Threonine Kinases metabolism
eIF-2 Kinase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 4
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 19137072
- Full Text :
- https://doi.org/10.1371/journal.pone.0004170