ArticleThe Journal of biological chemistry2016
The Different Conformational States of Tissue Transglutaminase Have Opposing Affects on Cell Viability.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 39 citations in OpenAlex.
- Astaxanthin effect on tissue transglutaminase expression in human neuronal differentiated stem cells exposed to hypoxia and hypoxia/reoxygenation.Scientific reports · 2026Article
- MMP-9 regulates disulphide isomerase activity of TGM2 to enhance fusion glycoprotein-mediated syncytium formation of respiratory syncytial virus.Protein & cell · 2026Article
- Distinct conformational states enable transglutaminase 2 to promote cancer cell survival versus cell death.Communications biology · 2024Article
- Effect of Ferulic Acid Loaded in Nanoparticle on Tissue Transglutaminase Expression Levels in Human Glioblastoma Cell Line.International journal of molecular sciences · 2024Article
- Membrane Association of the Short Transglutaminase Type 2 Splice Variant (TG2-S) Modulates Cisplatin Resistance in a Human Hepatocellular Carcinoma (HepG2) Cell Line.Current issues in molecular biology · 2024Article
- Canonical and truncated transglutaminase-2 regulate mucin-1 expression and androgen independency in prostate cancer cell lines.Cell death & disease · 2023Article
- Effect of Astaxanthin on Tissue Transglutaminase and Cytoskeletal Protein Expression in Amyloid-Beta Stressed Olfactory Ensheathing Cells: Molecular and Delayed Luminescence Studies.Antioxidants (Basel, Switzerland) · 2023Article
- The Impact ofInternational journal of molecular sciences · 2023Article
- Redox Properties, Bioactivity and Health Effects of Indicaxanthin, a Bioavailable Phytochemical fromAntioxidants (Basel, Switzerland) · 2022Review
- Effect of Unloaded and Curcumin-Loaded Solid Lipid Nanoparticles on Tissue Transglutaminase Isoforms Expression Levels in an Experimental Model of Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2022Article
- Evolving Experimental Techniques for Structure-Based Drug Design.The journal of physical chemistry. B · 2022Review
- Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation.Scientific reports · 2022Article
- Exploring the Role of Transglutaminase in Patients with Glioblastoma: Current Perspectives.OncoTargets and therapy · 2022Review
- Amyloid-Beta Induces Different Expression Pattern of Tissue Transglutaminase and Its Isoforms on Olfactory Ensheathing Cells: Modulatory Effect of Indicaxanthin.International journal of molecular sciences · 2021Article
- Role of Tissue Transglutaminase Catalytic and Guanosine Triphosphate-Binding Domains in Renal Cell Carcinoma Progression.ACS omega · 2020Article
- Moonlighting Proteins Are Important Players in Cancer Immunology.Frontiers in immunology · 2020Review
- The diamond anniversary of tissue transglutaminase: a protein of many talents.Drug discovery today · 2018Review
- Opening up about Tissue Transglutaminase: When Conformation Matters More than Enzymatic Activity.Med one · 2018Article
- Calcium-dependent activation of transglutaminase 2 by nanosecond pulsed electric fields.FEBS open bio · 2017Article
- Modulatory Effect of Natural Antioxidants on Tissue Transglutaminase Levels in Olfactory Ensheathing Cells Exposed to Amyloid-β: Integrated Biochemical and Computational Analysis.BioFactors (Oxford, England)Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tissue transglutaminase (tTG) is an acyltransferase/GTP-binding protein that contributes to the development of various diseases. In human cancer cells, tTG activates signaling pathways that promote cell growth and survival, whereas in other disorders (i.e. neurodegeneration), overexpression of tTG enhances cell death. Therefore, it is important to understand how tTG is differentially regulated and functioning to promote diametrically distinct cellular outcomes. Previous structural studies revealed that tTG adopts either a nucleotide-bound closed conformation or a transamidation-competent open conformation. Here we provide evidence showing that these different conformational states determine whether tTG promotes, or is detrimental to, cell survival, with the open conformation of the protein being responsible for inducing cell death. First, we demonstrate that a nucleotide binding-defective form of tTG, which has previously been shown to induce cell death, assumes an open conformation in solution as assessed by an enhanced sensitivity to trypsin digestion and by small angle x-ray scattering (SAXS) analysis. We next identify two pairs of intramolecular hydrogen bonds that, based on existing x-ray structures, are predicted to form between the most C-terminal β-barrel domain and the catalytic core domain of tTG. By disrupting these hydrogen bonds, we are able to generate forms of tTG that constitutively assume an open conformation and induce apoptosis. These findings provide important insights into how tTG participates in the pathogenesis of neurodegenerative diseases, particularly with regard to the actions of a C-terminal truncated form of tTG (TG-Short) that has been linked to such disorders and induces apoptosis by assuming an open-like conformation.
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What Socratic 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 Socratic graph.