Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis
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 isomeras...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/7/1842 |
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| author | Hideki Tatsukawa Kiyotaka Hitomi |
| author_facet | Hideki Tatsukawa Kiyotaka Hitomi |
| author_sort | Hideki Tatsukawa |
| collection | DOAJ |
| description | 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<sup>2+</sup> or other factors, TG2 adopts a Ca<sup>2+</sup>-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. |
| first_indexed | 2024-03-10T09:42:59Z |
| format | Article |
| id | doaj.art-3ee9eea37e6545c2b5e25db5f47cbf23 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T09:42:59Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3ee9eea37e6545c2b5e25db5f47cbf232023-11-22T03:31:02ZengMDPI AGCells2073-44092021-07-01107184210.3390/cells10071842Role of Transglutaminase 2 in Cell Death, Survival, and FibrosisHideki Tatsukawa0Kiyotaka Hitomi1Cellular Biochemistry Laboratory, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Nagoya 464-8601, Aichi, JapanCellular Biochemistry Laboratory, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research System, Nagoya 464-8601, Aichi, JapanTransglutaminase 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<sup>2+</sup> or other factors, TG2 adopts a Ca<sup>2+</sup>-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.https://www.mdpi.com/2073-4409/10/7/1842transglutaminasecrosslinkingTG2cell deathcell survivalmacrophage activation |
| spellingShingle | Hideki Tatsukawa Kiyotaka Hitomi Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis Cells transglutaminase crosslinking TG2 cell death cell survival macrophage activation |
| title | Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis |
| title_full | Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis |
| title_fullStr | Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis |
| title_full_unstemmed | Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis |
| title_short | Role of Transglutaminase 2 in Cell Death, Survival, and Fibrosis |
| title_sort | role of transglutaminase 2 in cell death survival and fibrosis |
| topic | transglutaminase crosslinking TG2 cell death cell survival macrophage activation |
| url | https://www.mdpi.com/2073-4409/10/7/1842 |
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