ArticleThe EMBO journal2024
The IRE1β-mediated unfolded protein response is repressed by the chaperone AGR2 in mucin producing cells.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Host metabolism shapes the intestinal microbiota: a top-down paradigm of environmental selection pressure.Gut microbes · 2026Review
- A regulatory circuit operated by KDELR1 and KDELR3 fine-tunes the composition of the early secretory pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Targeting endoplasmic reticulum stress in diabetic retinopathy: mechanistic insights and emerging therapies.Biological research · 2026Review
- Mucin 2 and unfolded protein response reshape the mucus barrier in inflammatory bowel disease (Review).Molecular medicine reports · 2026Review
- Diagnostic and prognostic biomarkers associated with histotype in advanced epithelial ovarian cancer.Scientific reports · 2025Article
- Agr2 in cancer and beyond: unraveling its role during protein synthesis, ER stress, and as a predictive biomarker.Molecular and cellular biochemistry · 2025Review
- Non-Canonical, Strongly Selective Protein Disulfide Isomerases as Anticancer Therapeutic Targets.Biomolecules · 2025Review
- DR5 Disulfide Bonding Functions as a Sensor and Effector of Protein Folding Stress.Molecular cancer research : MCR · 2025Article
- IRE1α and IRE1β Protect Intestinal Epithelium and Suppress Colorectal Tumorigenesis through Distinct Mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- Disrupting AGR2/IGF1 paracrine and reciprocal signaling for pancreatic cancer therapy.Cell reports. Medicine · 2025Article
- TMX5/TXNDC15, a natural trapping mutant of the PDI family is a client of the proteostatic factor ERp44.Life science alliance · 2024Article
- Review
- Essential roles of the unfolded protein response in intestinal physiology.eGastroenterology · 2024Review
- A genome-wide CRISPR/Cas9 screen identifies calreticulin as a selective repressor of ATF6α.eLife · 2024Article
- Emerging cell and molecular targets for treating mucus hypersecretion in asthma.Allergology international : official journal of the Japanese Society of Allergology · 2024Review
- Exploring the IRE1 interactome: From canonical signaling functions to unexpected roles.The Journal of biological chemistry · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Effector mechanisms of the unfolded protein response (UPR) in the endoplasmic reticulum (ER) are well-characterised, but how ER proteostasis is sensed is less well understood. Here, we exploited the beta isoform of the UPR transducer IRE1, that is specific to mucin-producing cells in order to gauge the relative regulatory roles of activating ligands and repressing chaperones of the specialised ER of goblet cells. Replacement of the stress-sensing luminal domain of endogenous IRE1α in CHO cells (normally expressing neither mucin nor IRE1β) with the luminal domain of IRE1β deregulated basal IRE1 activity. The mucin-specific chaperone AGR2 repressed IRE1 activity in cells expressing the domain-swapped IRE1β/α chimera, but had no effect on IRE1α. Introduction of the goblet cell-specific client MUC2 reversed AGR2-mediated repression of the IRE1β/α chimera. In vitro, AGR2 actively de-stabilised the IRE1β luminal domain dimer and formed a reversible complex with the inactive monomer. These features of the IRE1β-AGR2 couple suggest that active repression of IRE1β by a specialised mucin chaperone subordinates IRE1 activity to a proteostatic challenge unique to goblet cells, a challenge that is otherwise poorly recognised by the pervasive UPR transducers.
Indexed as
Identifiers
What OpenQuestion holds
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.