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IRE1 signaling increases PERK expression during chronic ER stress.
Gideon Ong1, Rosemund Ragetli1, Katarzyna Mnich2,3
1Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Cell Death & Disease
|April 18, 2024
Summary
The Unfolded Protein Response (UPR) adapts to stress. IRE1 signaling sustains PERK expression during prolonged ER stress, enhancing UPR plasticity and cellular survival.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- The Unfolded Protein Response (UPR) is a critical cellular pathway.
- UPR activation occurs due to Endoplasmic Reticulum (ER) stress from unfolded proteins.
- Key sensors IRE1, PERK, and ATF6 initiate UPR signaling to restore ER homeostasis.
Purpose of the Study:
- To investigate subtle signaling events fine-tuning the UPR.
- To explore cross-talk between UPR branches.
- To understand how UPR adapts to varying stress amplitudes and durations.
Main Methods:
- Investigated signaling pathways within the UPR.
- Focused on the interplay between IRE1 and PERK branches.
- Utilized experimental models to observe ER stress responses.
Main Results:
- Demonstrated cross-talk between IRE1 and PERK pathways.
- Showed that IRE1 signaling, via XBP1s, sustains PERK expression during prolonged ER stress.
- Identified a mechanism supporting UPR adaptiveness.
Conclusions:
- Cross-talk between UPR branches enhances signaling plasticity.
- This adaptiveness supports cellular survival under prolonged ER stress.
- Findings reveal novel regulatory mechanisms of the UPR.
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