IRE1 signaling increases PERK expression during chronic ER stress
Abstract The Unfolded Protein Response (UPR) is an essential cellular process activated by the accumulation of unfolded proteins within the Endoplasmic Reticulum (ER), a condition referred to as ER stress. Three ER anchored receptors, IRE1, PERK and ATF6 act as ER stress sensors monitoring the healt...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-06663-0 |
| _version_ | 1797199151838003200 |
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| author | Gideon Ong Rosemund Ragetli Katarzyna Mnich Bradley W. Doble Wafa Kammouni Susan E. Logue |
| author_facet | Gideon Ong Rosemund Ragetli Katarzyna Mnich Bradley W. Doble Wafa Kammouni Susan E. Logue |
| author_sort | Gideon Ong |
| collection | DOAJ |
| description | Abstract The Unfolded Protein Response (UPR) is an essential cellular process activated by the accumulation of unfolded proteins within the Endoplasmic Reticulum (ER), a condition referred to as ER stress. Three ER anchored receptors, IRE1, PERK and ATF6 act as ER stress sensors monitoring the health of the ER. Upon detection of ER stress, IRE1, PERK and ATF6 initiate downstream signaling pathways collectively referred to as the UPR. The overarching aim of the UPR is to restore ER homeostasis by reducing ER stress, however if that is not possible, the UPR transitions from a pro-survival to a pro-death response. While our understanding of the key signaling pathways central to the UPR is well defined, the same is not true of the subtle signaling events that help fine tune the UPR, supporting its ability to adapt to varying amplitudes or durations of ER stress. In this study, we demonstrate cross talk between the IRE1 and PERK branches of the UPR, wherein IRE1 via XBP1s signaling helps to sustain PERK expression during prolonged ER stress. Our findings suggest cross talk between UPR branches aids adaptiveness thereby helping to support the plasticity of UPR signaling responses. |
| first_indexed | 2024-04-24T07:11:12Z |
| format | Article |
| id | doaj.art-ce0b60685af34633bbe0b854e73cac1d |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-24T07:11:12Z |
| publishDate | 2024-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-ce0b60685af34633bbe0b854e73cac1d2024-04-21T11:32:01ZengNature Publishing GroupCell Death and Disease2041-48892024-04-0115411110.1038/s41419-024-06663-0IRE1 signaling increases PERK expression during chronic ER stressGideon Ong0Rosemund Ragetli1Katarzyna Mnich2Bradley W. Doble3Wafa Kammouni4Susan E. Logue5Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of ManitobaDepartment of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of ManitobaApoptosis Research Centre, University of GalwayDepartment of Paediatrics, Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences University of ManitobaDepartment of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of ManitobaDepartment of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of ManitobaAbstract The Unfolded Protein Response (UPR) is an essential cellular process activated by the accumulation of unfolded proteins within the Endoplasmic Reticulum (ER), a condition referred to as ER stress. Three ER anchored receptors, IRE1, PERK and ATF6 act as ER stress sensors monitoring the health of the ER. Upon detection of ER stress, IRE1, PERK and ATF6 initiate downstream signaling pathways collectively referred to as the UPR. The overarching aim of the UPR is to restore ER homeostasis by reducing ER stress, however if that is not possible, the UPR transitions from a pro-survival to a pro-death response. While our understanding of the key signaling pathways central to the UPR is well defined, the same is not true of the subtle signaling events that help fine tune the UPR, supporting its ability to adapt to varying amplitudes or durations of ER stress. In this study, we demonstrate cross talk between the IRE1 and PERK branches of the UPR, wherein IRE1 via XBP1s signaling helps to sustain PERK expression during prolonged ER stress. Our findings suggest cross talk between UPR branches aids adaptiveness thereby helping to support the plasticity of UPR signaling responses.https://doi.org/10.1038/s41419-024-06663-0 |
| spellingShingle | Gideon Ong Rosemund Ragetli Katarzyna Mnich Bradley W. Doble Wafa Kammouni Susan E. Logue IRE1 signaling increases PERK expression during chronic ER stress Cell Death and Disease |
| title | IRE1 signaling increases PERK expression during chronic ER stress |
| title_full | IRE1 signaling increases PERK expression during chronic ER stress |
| title_fullStr | IRE1 signaling increases PERK expression during chronic ER stress |
| title_full_unstemmed | IRE1 signaling increases PERK expression during chronic ER stress |
| title_short | IRE1 signaling increases PERK expression during chronic ER stress |
| title_sort | ire1 signaling increases perk expression during chronic er stress |
| url | https://doi.org/10.1038/s41419-024-06663-0 |
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