ArticleThe Journal of biological chemistry2011
Activation of extracellular transglutaminase 2 by thioredoxin.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 113 citations in OpenAlex.
- The TG2/LRP1 Pathway for T Cell Activation by Post-Translationally Modified Antigens.Immunological reviews · 2026Review
- Targeting injury-induced transglutaminase-2 activity with a cementoin-SLPI fusion protein: a novel therapeutic strategy for alkali-induced corneal injury.Journal of translational medicine · 2026Review
- Review
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- Gene-Environment Interactions in Celiac Disease: The Role of the Intestinal Epithelium.Lifestyle genomics · 2026Review
- Determining the Redox Potential of a Protein Disulfide Bond.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A dendritic cell population responsible for transglutaminase 2-mediated gluten antigen presentation in celiac disease.JCI insight · 2025Article
- ROMO1 overexpression protects the mitochondrial cysteinome from oxidations in aging.Nature communications · 2025Article
- Targeting transglutaminase 2: pathways to celiac disease therapies.Gastroenterology report · 2025Article
- Endoplasmic Reticulum Oxidative Stress Promotes Glutathione-Dependent Oxidation of Collagen-1A1 and Promotes Lung Fibroblast Activation.American journal of respiratory cell and molecular biology · 2024Article
- Structural and mechanistic analysis of CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Pathogenetic Contributions and Therapeutic Implications of Transglutaminase 2 in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation.Scientific reports · 2022Article
- Article
- Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease.International journal of molecular sciences · 2022Article
- An Unusual "OR" Gate for Allosteric Regulation of Mammalian Transglutaminase 2 in the Extracellular Matrix.Journal of the American Chemical Society · 2021Article
- Review
- Programmed Cell Death in the Small Intestine: Implications for the Pathogenesis of Celiac Disease.International journal of molecular sciences · 2021Review
- Transglutaminase 2 moderates the expansion of mouse abdominal aortic aneurysms.JVS-vascular science · 2021Article
- Interplay Between Gluten, HLA, Innate and Adaptive Immunity Orchestrates the Development of Coeliac Disease.Frontiers in immunology · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The mechanism of activation of transglutaminase 2 (TG2) in the extracellular matrix remains a fundamental mystery in our understanding of the biology of this multifunctional mammalian enzyme. Earlier investigations have highlighted the role of a disulfide bond formed by vicinal Cys residues in maintaining calcium-bound TG2 in an inactive state. Here, we have shown that the redox potential of this disulfide bond is approximately -190 mV, a high value for a disulfide bond in proteins. Consistent with this observation, TG2 activity in a freshly wounded fibroblast culture depends upon the redox potential of the environment. We sought to identify a physiological mechanism for the activation of oxidized TG2. With a k(cat)/K(m) of 1.6 μm(-1) min(-1), human thioredoxin (Trx) was a highly specific activator of oxidized human TG2. Trx-mediated activation of TG2 was blocked by PX-12, a small molecule Trx inhibitor that is undergoing clinical trials as a cancer chemotherapeutic agent. In a mixed culture containing fibroblasts and monocytic cells, interferon-γ stimulated Trx release from monocytes, which in turn activated TG2 around the fibroblasts. Recombinant human Trx could also activate extracellular TG2 in cryosections of human and mouse small intestinal biopsies. In addition to explaining how TG2 can be activated by dietary gluten in the small intestinal mucosa of celiac sprue patients, our findings reveal a new strategy for inhibiting the undesirable consequences of TG2 activity in this widespread, lifelong disease.
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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.