Tissue Transglutaminase: A Multifunctional and Multisite Regulator in Health and Disease

Authors

Zhouzhou Yao
Yuhua Fan
Lizhen Lin
Rodney E Kellems
Yang Xia

Language

English

Publication Date

1-1-2024

Journal

Physiological Reviews

DOI

10.1152/physrev.00003.2023

PMID

37712623

Abstract

Tissue transglutaminase (TG2) is a widely distributed multifunctional protein involved in a broad range of cellular and metabolic functions carried out in a variety of cellular compartments. In addition to transamidation, TG2 also functions as a Gα signaling protein, a protein disulfide isomerase (PDI), a protein kinase, and a scaffolding protein. In the nucleus, TG2 modifies histones and transcription factors. The PDI function catalyzes the trimerization and activation of heat shock factor-1 in the nucleus and regulates the oxidation state of several mitochondrial complexes. Cytosolic TG2 modifies proteins by the addition of serotonin or other primary amines and in this way affects cell signaling. Modification of protein-bound glutamines reduces ubiquitin-dependent proteasomal degradation. At the cell membrane, TG2 is associated with G protein-coupled receptors (GPCRs), where it functions in transmembrane signaling. TG2 is also found in the extracellular space, where it functions in protein cross-linking and extracellular matrix stabilization. Of particular importance in transglutaminase research are recent findings concerning the role of TG2 in gene expression, protein homeostasis, cell signaling, autoimmunity, inflammation, and hypoxia. Thus, TG2 performs a multitude of functions in multiple cellular compartments, making it one of the most versatile cellular proteins. Additional evidence links TG2 with multiple human diseases including preeclampsia, hypertension, cardiovascular disease, organ fibrosis, cancer, neurodegenerative diseases, and celiac disease. In conclusion, TG2 provides a multifunctional and multisite response to physiological stress.

Keywords

Humans, Protein Glutamine gamma Glutamyltransferase 2, GTP-Binding Proteins, Transglutaminases, Signal Transduction, Extracellular Matrix, hypoxia response, inflammatory response, multifunctional protein, stress response protein, transglutaminase 2

Published Open-Access

yes

Recommended Citation

Yao, Zhouzhou; Fan, Yuhua; Lin, Lizhen; et al., "Tissue Transglutaminase: A Multifunctional and Multisite Regulator in Health and Disease" (2024). Faculty, Staff and Student Publications. 5960.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5960