ArticleFrontiers in immunology2019
Thioredoxin Modulates Protein Arginine Deiminase 4 (PAD4)-Catalyzed Citrullination.
Article in Frontiers in immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Bilirubin reduces mortality in sepsis models by inhibiting NOX2-mediated formation of neutrophil extracellular traps.Redox report : communications in free radical research · 2026Article
- Anti-gingipain antibodies and ACE1 activity in rheumatoid arthritis: associations with disease activity and cardiovascular comorbidity in a cross-sectional study.Rheumatology international · 2026Article
- Mapping the Substrate Specificity Landscape of PAD2 and PAD4 Enzymes.Chembiochem : a European journal of chemical biology · 2026Article
- Metabolic and neuroimmune control of rheumatoid arthritis: therapeutic implications of FXR and α7-nAChR axes.Inflammopharmacology · 2026Review
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Lactoferrin and Thioredoxin in Rheumatoid Arthritis Are Associated with Fibrinogen but Not with Other Acute Phase Proteins.International journal of molecular sciences · 2025Article
- Review
- Serum thioredoxin and lactoferrin in rheumatoid arthritis and their association with rheumatoid factor.Journal of medical biochemistry · 2025Article
- Exploring Immune Redox Modulation in Bacterial Infections: Insights into Thioredoxin-Mediated Interactions and Implications for Understanding Host-Pathogen Dynamics.Antioxidants (Basel, Switzerland) · 2024Review
- Current insights into the role of citrullination in thrombosis.Current opinion in chemical biology · 2023Review
- The role of extracellular histones in COVID-19.Journal of internal medicine · 2023Review
- Exercise reduces the protein abundance of TXNIP and its interacting partner REDD1 in skeletal muscle: potential role for a PKA-mediated mechanism.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Article
- Biomarkers of autoimmunity and beta cell metabolism in type 1 diabetes.Frontiers in immunology · 2022Review
- The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases.Journal of innate immunity · 2022Review
- The role of SERPIN citrullination in thrombosis.Cell chemical biology · 2021Article
- PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- PAD4 takes charge during neutrophil activation: Impact of PAD4 mediated NET formation on immune-mediated disease.Journal of thrombosis and haemostasis : JTH · 2021Review
- Citrullination and PAD Enzyme Biology in Type 1 Diabetes - Regulators of Inflammation, Autoimmunity, and Pathology.Frontiers in immunology · 2021Review
- An interplay of structure and intrinsic disorder in the functionality of peptidylarginine deiminases, a family of key autoimmunity-related enzymes.Cellular and molecular life sciences : CMLS · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Protein citrullination is a post-translational modification catalyzed by the protein arginine deiminases (PADs). This modification plays a crucial role in the pathophysiology of numerous autoimmune disorders including RA. Recently, there has been a growing interest in investigating physiological regulators of PAD activity to understand the primary cause of the associated disorders. Apart from calcium, it is well-documented that a reducing environment activates the PADs. Although the concentration of thioredoxin (hTRX), an oxidoreductase that maintains the cellular reducing environment, is elevated in RA patients, its contribution toward RA progression or PAD activity has not been explored. Herein, we demonstrate that hTRX activates PAD4. Kinetic characterization of PAD4 using hTRX as the reducing agent yielded parameters that are comparable to those obtained with a routinely used non-physiological reducing agent, e.g., DTT, suggesting the importance of hTRX in PAD regulation under physiological conditions. Furthermore, we show that various hTRX mutants, including redox inactive hTRX variants, are capable of activating PAD4. This indicates a mechanism that does not require oxidoreductase activity. Indeed, we observed non-covalent interactions between PAD4 and hTRX variants, and propose that these redox-independent interactions are sufficient for hTRX-mediated PAD4 activation.
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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.