ArticleScience signaling2015
IRE1 prevents endoplasmic reticulum membrane permeabilization and cell death under pathological conditions.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- BIP orchestrates bidirectional ER protein trafficking via co-chaperone complexes.Cellular & molecular biology letters · 2026Article
- The Unfolded Protein Response-Novel Mechanisms, Challenges, and Key Considerations for Therapeutic Intervention.Cancers · 2025Review
- Spatial protein redistribution: wandering but not lost.Cellular and molecular life sciences : CMLS · 2025Review
- Somatic mutations in IRE1α regulate keratinocyte migration and survival by differentially activating Rho GTPases.Journal of cell science · 2025Article
- Less is better: various means to reduce protein load in the endoplasmic reticulum.The FEBS journal · 2025Review
- Molecular insights into cell signaling pathways in kidney stone formation.Urolithiasis · 2025Review
- Orexins in apoptosis: a dual regulatory role.Frontiers in cellular neuroscience · 2024Review
- The ER membrane protein complex restricts mitophagy by controlling BNIP3 turnover.The EMBO journal · 2024Article
- IRE1α regulates ROS and immune responses after UVB irradiation.Redox experimental medicine · 2024Article
- The ER membrane protein complex governs lysosomal turnover of a mitochondrial tail-anchored protein, BNIP3, to restrict mitophagy.bioRxiv : the preprint server for biology · 2023Article
- Establishment of chemically oligomerizable TAR DNA-binding protein-43 which mimics amyotrophic lateral sclerosis pathology in mammalian cells.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial␣membrane.The EMBO journal · 2021Article
- Reflux of Endoplasmic Reticulum proteins to the cytosol inactivates tumor suppressors.EMBO reports · 2021Article
- Cell death-associated lipid droplet protein CIDE-A is a noncanonical marker of endoplasmic reticulum stress.JCI insight · 2021Article
- Bcl-2 Family of Proteins in the Control of Mitochondrial Calcium Signalling: An Old Chap with New Roles.International journal of molecular sciences · 2021Review
- Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression.Annals of translational medicine · 2021Article
- Molecular Mechanisms behind Inherited Neurodegeneration of the Optic Nerve.Biomolecules · 2021Review
- The Structure, Activation and Signaling of IRE1 and Its Role in Determining Cell Fate.Biomedicines · 2021Review
- Pharmacological Inhibition of Inositol-Requiring Enzyme 1α RNase Activity Protects Pancreatic Beta Cell and Improves Diabetic Condition in Insulin Mutation-Induced Diabetes.Frontiers in endocrinology · 2021Article
- A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome.Laboratory investigation; a journal of technical methods and pathology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The endoplasmic reticulum (ER) has emerged as a critical regulator of cell survival. IRE1 is a transmembrane protein with kinase and RNase activities that is localized to the ER and that promotes resistance to ER stress. We showed a mechanism by which IRE1 conferred protection against ER stress-mediated cell death. IRE1 signaling prevented ER membrane permeabilization mediated by Bax and Bak and cell death in cells experiencing ER stress. Suppression of IRE1 signaling triggered by its kinase activity led to the accumulation of the BH3 domain-containing protein Bnip3, which in turn triggered the oligomerization of Bax and Bak in the ER membrane and ER membrane permeabilization. Consequently, in response to ER stress, cells deficient in IRE1 were susceptible to leakage of ER contents, which was associated with the accumulation of calcium in mitochondria, oxidative stress in the cytosol, and ultimately cell death. Our results reveal a role for IRE1 in preventing a cell death-initializing step that emanates from the ER and provide a potential target for treating diseases characterized by ER stress, including diabetes and Wolfram syndrome.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.