ArticleEMBO molecular medicine2019
Control of anterior GRadient 2 (AGR2) dimerization links endoplasmic reticulum proteostasis to inflammation.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Complementary intra- and extracellular AGR2 activities support epithelial ovarian cancer cell aggressiveness.Oncogene · 2026Article
- Ketogenic diet exacerbates DSS-induced colitis through a β-hydroxybutyrate-Thomasclavelia spiroformis-γδ17 T cell axis in mice.Nature communications · 2026Article
- A regulatory circuit operated by KDELR1 and KDELR3 fine-tunes the composition of the early secretory pathway.Cellular and molecular life sciences : CMLS · 2026Article
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- Effects of Charged Surface on Electrochemical Sensitivity to Protein Dimerization.Analytical chemistry · 2025Article
- Main genetic factors associated with inflammatory bowel diseases and their consequences on intestinal permeability: involvement in gut inflammation.Journal of gastroenterology · 2025Review
- 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
- Human bladder organoids model urinary tract infection and bacteriophage therapy.bioRxiv : the preprint server for biology · 2025Article
- A BioID-based approach uncovers the interactome of hexose-6-phosphate dehydrogenase in breast cancer cells and identifies anterior gradient protein 2 as an interacting partner.Cell & bioscience · 2025Article
- Stellate ganglia block reduces airway hyperresponsiveness with modulates the IKK/NF-κB/IL-4/IL-5/IL-13 pathway.Respiratory research · 2025Article
- Disrupting AGR2/IGF1 paracrine and reciprocal signaling for pancreatic cancer therapy.Cell reports. Medicine · 2025Article
- A High-Affinity Monoclonal Antibody Against the Pancreatic Ductal Adenocarcinoma Target, Anterior Gradient-2 (AGR2/PDIA17).Antibodies (Basel, Switzerland) · 2024Article
- Essential roles of the unfolded protein response in intestinal physiology.eGastroenterology · 2024Review
- Identification of immune-associated biomarkers of diabetes nephropathy tubulointerstitial injury based on machine learning: a bioinformatics multi-chip integrated analysis.BioData mining · 2024Article
- AGR2: The Covert Driver and New Dawn of Hepatobiliary and Pancreatic Cancer Treatment.Biomolecules · 2024Review
- AGR2-mediated unconventional secretion of 14-3-3ε and α-actinin-4, responsive to ER stress and autophagy, drives chemotaxis in canine mammary tumor cells.Cellular & molecular biology letters · 2024Article
- The IRE1β-mediated unfolded protein response is repressed by the chaperone AGR2 in mucin producing cells.The EMBO journal · 2024Article
- Expression Profiling along the Murine Intestine: Different Mucosal Protection Systems and Alterations inInternational journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
29 authors at 11 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anterior gradient 2 (AGR2) is a dimeric protein disulfide isomerase family member involved in the regulation of protein quality control in the endoplasmic reticulum (ER). Mouse AGR2 deletion increases intestinal inflammation and promotes the development of inflammatory bowel disease (IBD). Although these biological effects are well established, the underlying molecular mechanisms of AGR2 function toward inflammation remain poorly defined. Here, using a protein-protein interaction screen to identify cellular regulators of AGR2 dimerization, we unveiled specific enhancers, including TMED2, and inhibitors of AGR2 dimerization, that control AGR2 functions. We demonstrate that modulation of AGR2 dimer formation, whether enhancing or inhibiting the process, yields pro-inflammatory phenotypes, through either autophagy-dependent processes or secretion of AGR2, respectively. We also demonstrate that in IBD and specifically in Crohn's disease, the levels of AGR2 dimerization modulators are selectively deregulated, and this correlates with severity of disease. Our study demonstrates that AGR2 dimers act as sensors of ER homeostasis which are disrupted upon ER stress and promote the secretion of AGR2 monomers. The latter might represent systemic alarm signals for pro-inflammatory responses.
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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.