Transcriptional control of transglutaminase 2 expression in mouse apoptotic thymocytes

Sándor, Katalin; Dániel, Bence; Kiss, Beáta; Kovács, Fruzsina; Szondy, Zsuzsanna

doi:10.1016/j.bbagrm.2016.05.011

Cited by 11 publications

(6 citation statements)

References 148 publications

(199 reference statements)

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“…In addition, TG2 expression is directly downregulated by micro-RNA 19, which is responsible for the increased invasion and metastasis of colorectal cancer cells [ 73 ]. In addition, enhancer RNA molecules of TG2 expression were identified to regulate the recruitment of the transcriptional repressor CTCF in the intergenic region of thymocytes treated with retinoids and TGF-β to induce their death [ 74 ]. Furthermore, a recent review summarized the various potential binding sites of transcription factors and single-nucleotide polymorphisms of the TGM2 promoter using information obtained from the public database of chromatin immunoprecipitation sequencing [ 75 ].…”

Section: Regulation Of Tg2 Expression and Activitymentioning

confidence: 99%

Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis

Tatsukawa

Hitomi

2021

Cells

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Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme catalyzing the crosslinking between Gln and Lys residues and involved in various pathophysiological events. Besides this crosslinking activity, TG2 functions as a deamidase, GTPase, isopeptidase, adapter/scaffold, protein disulfide isomerase, and kinase. It also plays a role in the regulation of hypusination and serotonylation. Through these activities, TG2 is involved in cell growth, differentiation, cell death, inflammation, tissue repair, and fibrosis. Depending on the cell type and stimulus, TG2 changes its subcellular localization and biological activity, leading to cell death or survival. In normal unstressed cells, intracellular TG2 exhibits a GTP-bound closed conformation, exerting prosurvival functions. However, upon cell stimulation with Ca2+ or other factors, TG2 adopts a Ca2+-bound open conformation, demonstrating a transamidase activity involved in cell death or survival. These functional discrepancies of TG2 open form might be caused by its multifunctional nature, the existence of splicing variants, the cell type and stimulus, and the genetic backgrounds and variations of the mouse models used. TG2 is also involved in the phagocytosis of dead cells by macrophages and in fibrosis during tissue repair. Here, we summarize and discuss the multifunctional and controversial roles of TG2, focusing on cell death/survival and fibrosis.

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Section: Regulation Of Tg2 Expression and Activitymentioning

confidence: 99%

Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis

Tatsukawa

Hitomi

2021

Cells

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“…Zhu et al 31 compared the ability of H3K27ac and eRNA transcription to predict enhancer activity and revealed the latter was more representative. Sandor et al 39 determined whether the enhancers were functional by measuring the production of eRNAs in thymocytes. Previous study showed P53 regulated hundreds of eRNAs and Leveille et al localized p53-regulated enhancers by eRNA production 40 , 41 .…”

Section: Function Of Ernasmentioning

confidence: 99%

Enhancer RNAs (eRNAs): New Insights into Gene Transcription and Disease Treatment

et al. 2018

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Enhancers are cis-acting elements that have the ability to increase the expression of target genes. Recent studies have shown that enhancers can act as transcriptional units for the production of enhancer RNAs (eRNAs), which are hallmarks of activity enhancers and are involved in the regulation of gene transcription. The in-depth study of eRNAs is of great significance for us to better understand enhancer function and transcriptional regulation in various diseases. Therefore, eRNAs may be a potential therapeutic target for diseases. Here, we review the current knowledge of the characteristics of eRNAs, the molecular mechanisms of eRNAs action, as well as diseases related to dysregulation of eRNAs.

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“…No extensive amounts of these cells were found due to perfusion of the animals, but particular cells attached to the endothelium were existent. As TG2 can contribute to immune cell apoptosis and is upregulated during this process (Sandor et al 2016 ), we studied the presence of active caspase-3 in spinal cord EAE lesions. Only few cells immunopositive for the cleaved caspase-3 fragments (17/19 kDa) were found and single cells were co-labelled with TG2, while others were not (Fig.…”

Section: Resultsmentioning

confidence: 99%

Monocyte behaviour and tissue transglutaminase expression during experimental autoimmune encephalomyelitis in transgenic CX3CR1gfp/gfp mice

et al. 2016

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Leukocyte infiltration into the central nervous system (CNS) is a key pathological feature in multiple sclerosis (MS) and the MS animal model experimental autoimmune encephalomyelitis (EAE). Recently, preventing leukocyte influx into the CNS of MS patients is the main target of MS therapies and insight into cell behaviour in the circulation is needed for further elucidation of such therapies. In this study, we aimed at in vivo visualization of monocytes in a time-dependent manner during EAE. Using intravital two-photon microscopy (IVM), we imaged CX3CR1gfp/gfp mice during EAE, visualizing CX3CR1-GFP+ monocytes and their dynamics in the spinal cord vasculature. Our observations showed that intraluminal crawling of CX3CR1-GFP+ monocytes increased even before the clinical onset of EAE due to immunization of the animals. Furthermore, intraluminal crawling remained elevated during ongoing clinical disease. Besides, the displacement of these cells was larger during the peak of EAE compared to the control animals. In addition, we showed that the enzyme tissue transglutaminase (TG2), which is present in CNS-infiltrated cells in MS patients, is likewise found in CX3CR1-GFP+ monocytes in the spinal cord lesions and at the luminal side of the vasculature during EAE. It might thereby contribute to adhesion and crawling of monocytes, facilitating extravasation into the CNS. Thus, we put forward that interference with monocyte adhesion, by e.g. inhibition of TG2, should be applied at a very early stage of EAE and possibly MS, to effectively combat subsequent pathology.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-016-2359-0) contains supplementary material, which is available to authorized users.

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Transcriptional control of transglutaminase 2 expression in mouse apoptotic thymocytes

Cited by 11 publications

References 148 publications

Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis

Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis

Enhancer RNAs (eRNAs): New Insights into Gene Transcription and Disease Treatment

Monocyte behaviour and tissue transglutaminase expression during experimental autoimmune encephalomyelitis in transgenic CX3CR1gfp/gfp mice

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