ArticleOncogene2017
Transamidase site-targeted agents alter the conformation of the transglutaminase cancer stem cell survival protein to reduce GTP binding activity and cancer stem cell survival.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- From Signaling Pathways to Combination Therapy: Bioactive Compounds against Cancer Stem Cells.Stem cell reviews and reports · 2026Review
- Human Transglutaminases: Updated Insights into Activation Mechanisms, Allosteric Regulation and Disease.International journal of molecular sciences · 2026Review
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Novel PROTACs targeting tissue transglutaminase (TG2) suppress tumorigenicity of ovarian cancer cells.European journal of medicinal chemistry · 2026Article
- Article
- Pharmacological inhibition of astrocytic transglutaminase 2 facilitates the expression of a neurosupportive astrocyte reactive phenotype in association with increased histone acetylation.bioRxiv : the preprint server for biology · 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
- Biological Implications and Functional Significance of Transglutaminase Type 2 in Nervous System Tumors.Cells · 2024Review
- Pathogenetic Contributions and Therapeutic Implications of Transglutaminase 2 in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Cell-Impermeable Inhibitors Confirm That Intracellular Human Transglutaminase 2 Is Responsible for the Transglutaminase-Associated Cancer Phenotype.International journal of molecular sciences · 2023Article
- Discovery and Characterization of PROTACs Targeting Tissue Transglutaminase (TG2).Journal of medicinal chemistry · 2023Article
- Transglutaminase 2 associated with PI3K and PTEN in a membrane-bound signalosome platform blunts cell death.Cell death & disease · 2023Article
- Novel irreversible peptidic inhibitors of transglutaminase 2.RSC medicinal chemistry · 2023Article
- The war on hTG2: warhead optimization in small molecule human tissue transglutaminase inhibitors.RSC medicinal chemistry · 2023Article
- Peptidic Inhibitors and a Fluorescent Probe for the Selective Inhibition and Labelling of Factor XIIIa Transglutaminase.Molecules (Basel, Switzerland) · 2023Article
- The Impact ofInternational journal of molecular sciences · 2023Article
- The transglutaminase 2 cancer cell survival factor maintains mTOR activity to drive an aggressive cancer phenotype.Molecular carcinogenesis · 2023Article
- A Multidisciplinary Approach Establishes a Link between Transglutaminase 2 and the Kv10.1 Voltage-Dependent KCancers · 2022Article
- Review
- Sulforaphane covalently interacts with the transglutaminase 2 cancer maintenance protein to alter its structure and suppress its activity.Molecular carcinogenesis · 2022Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Type 2 transglutaminase (TG2) is an important cancer stem cell survival protein that exists in open and closed conformations. The major intracellular form is the closed conformation that functions as a GTP-binding GTPase and is required for cancer stem cell survival. However, at a finite rate, TG2 transitions to an open conformation that exposes the transamidase catalytic site involved in protein-protein crosslinking. The activities are mutually exclusive, as the closed conformation has GTP binding/GTPase activity, and the open conformation transamidase activity. We recently showed that GTP binding, but not transamidase activity, is required for TG2-dependent cancer stem cell invasion, migration and tumour formation. However, we were surprised that transamidase site-specific inhibitors reduce cancer stem cell survival. We now show that compounds NC9, VA4 and VA5, which react exclusively at the TG2 transamidase site, inhibit both transamidase and GTP-binding activities. Transamidase activity is inhibited by direct inhibitor binding at the transamidase site, and GTP binding is blocked because inhibitor interaction at the transamidase site locks the protein in the extended/open conformation to disorganize/inactivate the GTP binding/GTPase site. These findings suggest that transamidase site-specific inhibitors can inhibit GTP binding/signalling by driving a conformation change that disorganizes the TG2 GTP binding to reduce TG2-dependent signalling, and that drugs designed to target this site may be potent anti-cancer agents.
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