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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Internet ISSN: 2073-4409 (Electronic) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI

Aminoacyltransferases/*genetics ; Carbon-Nitrogen Lyases/*genetics ; Fibrosis/*enzymology ; GTP-Binding Proteins/*genetics ; Inflammation/*enzymology ; Protein Disulfide-Isomerases/*genetics ; Transglutaminases/*genetics; Alternative Splicing ; Aminoacyltransferases/immunology ; Animals ; Calcium/immunology ; Calcium/metabolism ; Carbon-Nitrogen Lyases/immunology ; Cell Death ; Cell Survival ; Fibrosis/genetics ; Fibrosis/immunology ; Fibrosis/pathology ; GTP-Binding Proteins/immunology ; Gene Expression ; Guanosine Triphosphate/immunology ; Guanosine Triphosphate/metabolism ; Humans ; Inflammation/genetics ; Inflammation/immunology ; Inflammation/pathology ; Isoenzymes/genetics ; Isoenzymes/immunology ; Macrophages/enzymology ; Macrophages/immunology ; Phagocytosis/genetics ; Protein Disulfide-Isomerases/immunology ; Protein Glutamine gamma Glutamyltransferase 2 ; Transglutaminases/immunology

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 Ca ²⁺ or other factors, TG2 adopts a Ca ²⁺ -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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Keywords: TG2; cell death; cell survival; crosslinking; fibrosis; macrophage activation; transglutaminase

0 (Isoenzymes)
86-01-1 (Guanosine Triphosphate)
EC 2.3.2.- (Aminoacyltransferases)
EC 2.3.2.- (transamidases)
EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2)
EC 2.3.2.13 (Transglutaminases)
EC 3.6.1.- (GTP-Binding Proteins)
EC 4.3.- (Carbon-Nitrogen Lyases)
EC 4.3.- (isopeptidase)
EC 5.3.4.1 (Protein Disulfide-Isomerases)
SY7Q814VUP (Calcium)

Date Created: 20210807 Date Completed: 20211027 Latest Revision: 20211204

20221213

PMC8307792

10.3390/cells10071842

34360011