Divergent effects of PERK and IRE1 signaling on cell viability.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004170&type=printable |
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| _version_ | 1850240821168701440 |
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| author | Jonathan H Lin Han Li Yuhong Zhang David Ron Peter Walter |
| author_facet | Jonathan H Lin Han Li Yuhong Zhang David Ron Peter Walter |
| author_sort | Jonathan H Lin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3d8830e6a6b8423f9752c7e38b894ac7 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-3d8830e6a6b8423f9752c7e38b894ac72025-08-20T02:00:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0141e417010.1371/journal.pone.0004170Divergent effects of PERK and IRE1 signaling on cell viability.Jonathan H LinHan LiYuhong ZhangDavid RonPeter WalterProtein 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004170&type=printable |
| spellingShingle | Jonathan H Lin Han Li Yuhong Zhang David Ron Peter Walter Divergent effects of PERK and IRE1 signaling on cell viability. PLoS ONE |
| title | Divergent effects of PERK and IRE1 signaling on cell viability. |
| title_full | Divergent effects of PERK and IRE1 signaling on cell viability. |
| title_fullStr | Divergent effects of PERK and IRE1 signaling on cell viability. |
| title_full_unstemmed | Divergent effects of PERK and IRE1 signaling on cell viability. |
| title_short | Divergent effects of PERK and IRE1 signaling on cell viability. |
| title_sort | divergent effects of perk and ire1 signaling on cell viability |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0004170&type=printable |
| work_keys_str_mv | AT jonathanhlin divergenteffectsofperkandire1signalingoncellviability AT hanli divergenteffectsofperkandire1signalingoncellviability AT yuhongzhang divergenteffectsofperkandire1signalingoncellviability AT davidron divergenteffectsofperkandire1signalingoncellviability AT peterwalter divergenteffectsofperkandire1signalingoncellviability |