ArticleThe Journal of biological chemistry2017
Thioredoxin-1 Selectively Activates Transglutaminase 2 in the Extracellular Matrix of the Small Intestine: IMPLICATIONS FOR CELIAC DISEASE.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- A dendritic cell population responsible for transglutaminase 2-mediated gluten antigen presentation in celiac disease.JCI insight · 2025Article
- Targeting transglutaminase 2: pathways to celiac disease therapies.Gastroenterology report · 2025Article
- Distinct conformational states enable transglutaminase 2 to promote cancer cell survival versus cell death.Communications biology · 2024Article
- Structural and mechanistic analysis of CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- Review
- Inhibition of Transglutaminase 2 as a Therapeutic Strategy in Celiac Disease-In Vitro Studies in Intestinal Cells and Duodenal Biopsies.International journal of molecular sciences · 2023Article
- LRP-1 links post-translational modifications to efficient presentation of celiac disease-specific T cell antigens.Cell chemical biology · 2023Article
- Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy.International journal of molecular sciences · 2022Review
- 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
- Programmed Cell Death in the Small Intestine: Implications for the Pathogenesis of Celiac Disease.International journal of molecular sciences · 2021Review
- Through the back door: Unconventional protein secretion.Cell surface (Amsterdam, Netherlands) · 2020Review
- Paracrine regulation and improvement of β-cell function by thioredoxin.Redox biology · 2020Article
- Structures of Human Transglutaminase 2: Finding Clues for Interference in Cross-linking Mediated Activity.International journal of molecular sciences · 2020Review
- Allosteric disulphide bonds as reversible mechano-sensitive switches that control protein functions in the vasculature.Biophysical reviews · 2019Review
- Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation.The Journal of biological chemistry · 2019Review
- In Vivo Measurement of Redox-Regulated TG2 Activity.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Transglutaminases in Monocytes and Macrophages.Medical sciences (Basel, Switzerland) · 2018Review
- Cystamine and cysteamine as inhibitors of transglutaminase activityBioscience reports · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Transglutaminase 2 (TG2) catalyzes transamidation or deamidation of its substrates and is ordinarily maintained in a catalytically inactive state in the intestine and other organs. Aberrant TG2 activity is thought to play a role in celiac disease, suggesting that a better understanding of TG2 regulation could help to elucidate the mechanistic basis of this malady. Structural and biochemical analysis has led to the hypothesis that extracellular TG2 activation involves reduction of an allosteric disulfide bond by thioredoxin-1 (TRX), but cellular and in vivo evidence for this proposal is lacking. To test the physiological relevance of this hypothesis, we first showed that macrophages exposed to pro-inflammatory stimuli released TRX in sufficient quantities to activate their extracellular pools of TG2. By using the C35S mutant of TRX, which formed a metastable mixed disulfide bond with TG2, we demonstrated that these proteins specifically recognized each other in the extracellular matrix of fibroblasts. When injected into mice and visualized with antibodies, we observed the C35S TRX mutant bound to endogenous TG2 as its principal protein partner in the small intestine. Control experiments showed no labeling of TG2 knock-out mice. Intravenous administration of recombinant TRX in wild-type mice, but not TG2 knock-out mice, led to a rapid rise in intestinal transglutaminase activity in a manner that could be inhibited by small molecules targeting TG2 or TRX. Our findings support the potential pathophysiological relevance of TRX in celiac disease and establish the Cys
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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.