ArticleEMBO reports2018
TG2 regulates the heat-shock response by the post-translational modification of HSF1.
Article in EMBO reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Transglutaminase 2 regulates innate immunity: mechanisms and therapeutic implications.Oncoimmunology · 2026Review
- Heat-Inactivated Selenium Nanoparticle-EnrichedMicroorganisms · 2026Article
- Removal or inhibition of transglutaminase 2 decreases cellular stress, supporting tissue preservation, and recovery after SCI.Acta neuropathologica communications · 2025Article
- Epigenetic modulation of RIPK3 by transglutaminase 2-dependent serotonylation of H3K4me3 affects necroptosis.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- Transglutaminase 2 Regulates HSF1 Gene Expression in the Acute Phase of Fish Optic Nerve Regeneration.International journal of molecular sciences · 2024Article
- The Role of Transglutaminase 2 in Cancer: An Update.International journal of molecular sciences · 2024Review
- Transglutaminase 2 regulates endothelial cell calcification via IL-6-mediated autophagy.Frontiers in pharmacology · 2024Article
- Immunomodulatory effects of cysteamine and its potential use as a host-directed therapy for tuberculosis.Frontiers in immunology · 2024Article
- Transglutaminase Type 2-MITF axis regulates phenotype switching in skin cutaneous melanoma.Cell death & disease · 2023Article
- Type 2 transglutaminase in the nucleus: the new epigenetic face of a cytoplasmic enzyme.Cellular and molecular life sciences : CMLS · 2023Review
- The STING/TBK1/IRF3/IFN type I pathway is defective in cystic fibrosis.Frontiers in immunology · 2023Article
- Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells.JCI insight · 2022Article
- HIF1, HSF1, and NRF2: Oxidant-Responsive Trio Raising Cellular Defenses and Engaging Immune System.Chemical research in toxicology · 2022Review
- Article
- Hsf1 promotes hematopoietic stem cell fitness and proteostasis in response to ex vivo culture stress and aging.Cell stem cell · 2021Article
- Autophagy in major human diseases.The EMBO journal · 2021Review
- The Multifaceted Role of HSF1 in Pathophysiology: Focus on Its Interplay with TG2.International journal of molecular sciences · 2021Review
- Transglutaminase Type 2 regulates the Wnt/β-catenin pathway in vertebrates.Cell death & disease · 2021Article
- Discovery and validation of candidate SNP markers associated to heat stress response in pregnant ewes managed inside a climate-controlled chamber.Tropical animal health and production · 2020Article
Corrections and comments
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Authors and funding
18 authors at 8 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat-shock factor 1 (HSF1) is the master transcription factor that regulates the response to proteotoxic stress by controlling the transcription of many stress-responsive genes including the heat-shock proteins. Here, we show a novel molecular mechanism controlling the activation of HSF1. We demonstrate that transglutaminase type 2 (TG2), dependent on its protein disulphide isomerase activity, triggers the trimerization and activation of HSF1 regulating adaptation to stress and proteostasis impairment. In particular, we find that TG2 loss of function correlates with a defect in the nuclear translocation of HSF1 and in its DNA-binding ability to the HSP70 promoter. We show that the inhibition of TG2 restores the unbalance in HSF1-HSP70 pathway in cystic fibrosis (CF), a human disorder characterized by deregulation of proteostasis. The absence of TG2 leads to an increase of about 40% in CFTR function in a new experimental CF mouse model lacking TG2. Altogether, these results indicate that TG2 plays a key role in the regulation of cellular proteostasis under stressful cellular conditions through the modulation of the heat-shock response.
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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.