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

Cells

卷:10

Hideki Tatsukawa¹  Kiyotaka Hitomi¹ 

[1] Cellular Biochemistry Laboratory, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Nagoya 464-8601, Aichi, Japan;

关键词: transglutaminase;    crosslinking;    TG2;    cell death;    cell survival;    macrophage activation;   

DOI  :  10.3390/cells10071842

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown