ArticleNature2009
The unfolded protein response signals through high-order assembly of Ire1.
Article in Nature, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 380 papers, 1 of them a synthesis that pooled it.
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
380 citing papers in PubMed, 1 synthesis or guideline pooled it, 664 citations in OpenAlex.
- ER stress as a trigger of UPR and ER-phagy in cancer growth and spread.Frontiers in oncology · 2022Pooled it
- XBP1 signaling from tumor metabolic stress to myeloid driven immunotherapy resistance (Review).International journal of molecular medicine · 2026Review
- TUSC3 serves as a rate-limiting gatekeeper of a glycan-mediated ER triage checkpoint for BMP4/Dpp.Cell reports · 2026Article
- Disruption of thePathogens (Basel, Switzerland) · 2026Article
- Pyrazolylpyrimidinamines Decorated via Petasis Reaction as Small-Molecule Activators of the RNA-Degrading Ribonuclease IRE1α.ACS bio & med chem Au · 2026Article
- Chemically-induced degradation of the endoplasmic-reticulum stress sensor IRE1 by a VHL-recruiting chimera.Nature communications · 2025Article
- Defining the role of β-cell IRE1α/XBP1 pathway and its gene regulatory network components in non-obese diabetic mice.Nature communications · 2025Article
- Molecular mechanisms mediated by liquid-liquid phase separation in chronic liver disease progression.iScience · 2025Review
- TUSC3 serves as a rate-limiting gatekeeper of a glycan-mediated ER Triage Checkpoint for BMP4/Dpp.bioRxiv : the preprint server for biology · 2025Article
- Harnessing indole scaffolds to identify small-molecule IRE1α inhibitors modulating XBP1 mRNA splicing.Nature communications · 2025Article
- A multichaperone condensate enhances protein folding in the endoplasmic reticulum.Nature cell biology · 2025Article
- Optogenetic Clustering of Human IRE1 Reveals Differential Regulation of Transcription and mRNA Splice Isoform Abundance by the UPR.bioRxiv : the preprint server for biology · 2025Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Identification of a Selective Pharmacologic IRE1/XBP1s Activator with Enhanced Tissue Exposure.ACS chemical biology · 2025Article
- A nonenzymatic dependency on inositol-requiring enzyme 1 controls cancer cell cycle progression and tumor growth.PLoS biology · 2025Article
- Geminivirus βV1 protein activates bZIP17/28-mediated UPR signaling to facilitate viral pathogenicity but its activity is attenuated by autophagic degradation in plants.Plant communications · 2025Article
- The role of the ER stress sensor IRE1 in cardiovascular diseases.Molecular and cellular biochemistry · 2025Review
- Endoplasmic Reticular Stress and Pathogenesis of Experimental Colitis: Mechanism of Action of 5-Amino Salicylic Acid.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2025Article
- Inositol-requiring enzyme 1 alpha is essential for dentinogenesis.Frontiers in physiology · 2025Article
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
320 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant folding of proteins in the endoplasmic reticulum activates the bifunctional transmembrane kinase/endoribonuclease Ire1. Ire1 excises an intron from HAC1 messenger RNA in yeasts and Xbp1 messenger RNA in metozoans encoding homologous transcription factors. This non-conventional mRNA splicing event initiates the unfolded protein response, a transcriptional program that relieves the endoplasmic reticulum stress. Here we show that oligomerization is central to Ire1 function and is an intrinsic attribute of its cytosolic domains. We obtained the 3.2-A crystal structure of the oligomer of the Ire1 cytosolic domains in complex with a kinase inhibitor that acts as a potent activator of the Ire1 RNase. The structure reveals a rod-shaped assembly that has no known precedence among kinases. This assembly positions the kinase domain for trans-autophosphorylation, orders the RNase domain, and creates an interaction surface for binding of the mRNA substrate. Activation of Ire1 through oligomerization expands the mechanistic repertoire of kinase-based signalling receptors.
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.