Transglutaminase 2 regulates terminal erythroid differentiation via cross-linking activity

Yingying Zhang; Lifang Shi; Lifang Shi; Ke Yang; Xuehui Liu; Xiang Lv

doi:10.3389/fcell.2023.1183176

Frontiers in Cell and Developmental Biology (Apr 2023)

Transglutaminase 2 regulates terminal erythroid differentiation via cross-linking activity

Yingying Zhang,
Lifang Shi,
Lifang Shi,
Ke Yang,
Xuehui Liu,
Xiang Lv

Affiliations

Yingying Zhang: State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Lifang Shi: State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Lifang Shi: Changping Center for Disease Control and Prevention, Beijing, China
Ke Yang: State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Xuehui Liu: State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
Xiang Lv: State Key Laboratory of Medical Molecular Biology, Haihe Laboratory of Cell Ecosystem, Department of Pathophysiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

DOI: https://doi.org/10.3389/fcell.2023.1183176
Journal volume & issue: Vol. 11

Abstract

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Transglutaminase 2 (TGM2) is a versatile enzyme that modulates cell survival and differentiation. However, its role in terminal erythroid differentiation is poorly understood. In this study, we investigated the function of TGM2 in primary fetal liver erythroid differentiation. We predicted TGM2 as an upstream regulator via ingenuity pathway analysis (IPA), and found that its expression was increased at both RNA and protein level during terminal erythroid differentiation. TGM2 cross-linking activity inhibitors GK921 and Z-DON suppressed erythroid maturation and enucleation, while its GTPase inhibitor LDN27219 had no such effect. Z-DON treatment arrested differentiation at basophilic erythroblast stage, and interfered with cell cycle progression. RT-PCR demonstrated decreased GATA-1 and KLF1, and disarranged cyclin, CDKI and E2F family genes expression after Z-DON treatment. In conclusion, TGM2 regulates terminal erythroid differentiation through its cross-linking enzyme activity.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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