ArticleThe Journal of biological chemistry2012
Ataxia-Telangiectasia, Mutated (ATM)/Nuclear Factor κ light chain enhancer of activated B cells (NFκB) signaling controls basal and DNA damage-induced transglutaminase 2 expression.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 72 citations in OpenAlex.
- OV16 Improves Radiation-Induced Intestinal Injury by Targeting Transglutaminase 2.Molecules (Basel, Switzerland) · 2026Article
- The Role of the TG2-GPR56 Complex in Cutaneous Squamous Cell Carcinoma (CSCC) Aggression and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- Transglutaminase 2 exacerbates ovarian cancer survival by directly inactivating GSK3β.Cell death & disease · 2026Article
- TGM2 Regulates Radiosensitivity via POGZ-Mediated Repair of DNA Double-Strand Breaks in Cervical Cancer.Cancer science · 2026Article
- Transglutaminase 2 nuclear localization enhances glioblastoma radiation resistance.Discover oncology · 2025Article
- Transglutaminase 2 in breast cancer metastasis and drug resistance.Frontiers in cell and developmental biology · 2024Review
- Transglutaminase-2 mediates acquisition of neratinib resistance in metastatic breast cancer.Molecular biomedicine · 2022Article
- Article
- Nuclear Transglutaminase 2 interacts with topoisomerase II⍺ to promote DNA damage repair in lung cancer cells.Journal of experimental & clinical cancer research : CR · 2021Article
- CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα/ATM-p73 axis in bladder cancer.Molecular cancer · 2021Article
- Transglutaminase 2 takes center stage as a cancer cell survival factor and therapy target.Molecular carcinogenesis · 2019Article
- C/EBPβ enhances platinum resistance of ovarian cancer cells by reprogramming H3K79 methylation.Nature communications · 2018Article
- ATM is required for SOD2 expression and homeostasis within the mammary gland.Breast cancer research and treatment · 2017Article
- Transglutaminase 2 overexpression induces depressive-like behavior and impaired TrkB signaling in mice.Molecular psychiatry · 2017Article
- The Breast Cancer Tumor Suppressor TRIM29 Is Expressed via ATM-dependent Signaling in Response to Hypoxia.The Journal of biological chemistry · 2016Article
- PARP3 controls TGFβ and ROS driven epithelial-to-mesenchymal transition and stemness by stimulating a TG2-Snail-E-cadherin axis.Oncotarget · 2016Article
- Transglutaminase 2 contributes to a TP53-induced autophagy program to prevent oncogenic transformation.eLife · 2016Article
- Mutual amplification of HNF4α and IL-1R1 composes an inflammatory circuit in Helicobacter pylori associated gastric carcinogenesis.Oncotarget · 2016Article
- Compensatory Increase of Transglutaminase 2 Is Responsible for Resistance to mTOR Inhibitor Treatment.PloS one · 2016Article
- Transglutaminase is a tumor cell and cancer stem cell survival factor.Molecular carcinogenesis · 2015Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that cross-links proteins and its overexpression, linked to a drug resistant phenotype, is commonly observed in cancer cells. Further, up-regulation of TG2 expression occurs during response to various forms of cell stress; however, the molecular mechanisms that drive inducible expression of the TG2 gene (TGM2) require elucidation. Here we show that genotoxic stress induces TG2 expression through the Ataxia-Telangiectasia, Mutated (ATM)/Nuclear Factor κ light chain enhancer of activated B cells (NFκB) signaling pathway. We further document that NFκB is both necessary and sufficient to drive constitutive TG2 expression in cultured cell lines. Additionally, shRNA-mediated knockdown or pharmacological inhibition of the ATM kinase results in reduced constitutive TG2 expression and NFκB transcriptional activity. We document that the NFκB subunit p65 (RelA) interacts with two independent consensus NFκB binding sites within the TGM2 promoter, that mutation of either site or pharmacological inhibition of NFκB reduces TGM2 promoter activity, and genotoxic stress drives heightened association of p65 with the TGM2 promoter. Finally, we observed that knockdown of either p65 or ATM in MDA-MB-468 breast cancer cells expressing recombinant TG2 partially reduces resistance to doxorubicin, indicating that the drug resistance linked to overexpression of TG2 functions, in part, through p65 and ATM. This work establishes a novel ATM-dependent signaling loop where TG2 and NFκB activate each other resulting in sustained activation of NFκB and acquisition of a drug-resistant phenotype.
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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.