Abstract
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.
Highlights
Transglutaminases (TGase) are multifunctional enzymes and constitute a family of eight isozymes designated as blood coagulation factor XIII and TG1–7
We focus on the role of Transglutaminase 2 (TG2) in cell death, macrophage activation, and tissue repair processes, which are involved in several pathogeneses, including tissue injury, inflammation, and fibrosis
We previously demonstrated that TG2 transamidase activity significantly increases in the nucleus of hepatocytes treated with alcohol or free fatty acid, promoting the crosslinking and inactivation of Sp1
Summary
Transglutaminases (TGase) are multifunctional enzymes and constitute a family of eight isozymes designated as blood coagulation factor XIII and TG1–7 In this family, TG2 is widely distributed and involved in multiple biological processes. TG2 is detected across the body, including the blood, extracellular spaces, and intracellular compartments of most tissues It is involved in cell death, growth, and differentiation as well as tissue repair by tissue remodeling/wound healing and ECM assembly [5]. We focus on the role of TG2 in cell death, macrophage activation, and tissue repair processes, which are involved in several pathogeneses, including tissue injury, inflammation, and fibrosis. Cells 2021, 10, 1842 cell death, macrophage activation, and tissue repair processes, which are involved in several pathogeneses, including tissue injury, inflammation, and fibrosis.
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