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The UPRosome - decoding novel biological outputs of IRE1α function
Hery Urra1,2,3, Philippe Pihán4,2,3, Claudio Hetz1,2,3,5
1Biomedical Neuroscience Institute (BNI), Faculty of Medicine, University of Chile, Santiago 8380453, Chile chetz@med.uchile.cl hery.urra@ug.uchile.cl.
Journal of Cell Science
|August 14, 2020
Summary
The unfolded protein response (UPR) sensor IRE1α, part of the UPRosome complex, regulates cell fate during ER stress. Bioinformatics analysis reveals its interactions extend to cell cycle, viral response, and immune pathways, uncovering new disease relevance.
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- Endoplasmic reticulum (ER) stress arises from misfolded proteins, activating the unfolded protein response (UPR) to restore proteostasis or induce apoptosis.
- IRE1α (ERN1) is a key sensor in the UPR, regulating cellular responses to ER stress.
- The UPRosome, a multi-protein complex, modulates IRE1α activity and pathway crosstalk.
Purpose of the Study:
- To theoretically analyze the biological significance of the UPRosome complex.
- To systematically identify and functionally characterize IRE1α interactome using bioinformatics.
- To explore novel signaling outputs and disease relevance of IRE1α.
Main Methods:
- Theoretical analysis of UPRosome function.
- Systematic bioinformatics analysis of IRE1α interactome data.
- Functional enrichment clustering of identified protein-protein interactions.
Main Results:
- The UPRosome complex plays a crucial role in regulating IRE1α activity and integrating various cellular pathways.
- Bioinformatic analysis identified novel IRE1α interactions beyond canonical UPR functions.
- IRE1α partners are involved in cell cycle, transport, differentiation, viral infection response, and immune response.
Conclusions:
- IRE1α's regulatory network extends beyond ER stress, impacting diverse cellular processes.
- Understanding the full spectrum of IRE1α interactors is vital for uncovering new signaling mechanisms.
- This research highlights the UPRosome's broad relevance to human diseases and potential therapeutic targets.
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