TRIM21 Regulates Virus-Induced Cell Pyroptosis through Polyubiquitination of ISG12a

被引：10

作者：

Guo, Mengmeng ^{[1
]}

Cao, Wenyan ^{[1
]}

Chen, Shengwen ^{[1
]}

Tian, Renyun ^{[1
]}

Xue, Binbin ^{[1
]}

Wang, Luoling ^{[1
]}

Liu, Qian ^{[1
]}

Deng, Rilin ^{[1
]}

Wang, Xintao ^{[1
]}

Wang, Zhenghao ^{[1
]}

Zhang, Yingdan ^{[1
]}

Yang, Di ^{[1
]}

Zuo, Chaohui ^{[2
]}

Li, Guangdi ^{[3
]}

Tang, Songqing ^{[1
]}

Zhu, Haizhen ^{[1
,2
]}

机构：

[1] Hunan Univ, Inst Pathogen Biol & Immunol Coll Biol, Hunan Prov Key Lab Med Virol, State Key Lab Chemo Biosensing & Chemometr, Changsha, Peoples R China

[2] Hunan Canc Hosp, Res Ctr Canc Prevent & Treatment, Translat Med Res Ctr Liver Canc, Changsha, Peoples R China

[3] Cent South Univ, Xiangya Sch Publ Hlth, Changsha, Hunan, Peoples R China

来源：

JOURNAL OF IMMUNOLOGY | 2022年 / 209卷 / 10期

基金：

中国国家自然科学基金;

关键词：

HEPATITIS-C VIRUS; INFLAMMATORY CASPASES; GASDERMIN D; UBIQUITINATION; REPLICATION; DEGRADATION; METHYLATION; ACTIVATION; CLEAVAGE; DEATH;

D O I：

10.4049/jimmunol.2200163

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Pyroptosis is a form of regulated cell death mediated by the gasdermin protein family. During virus infection, cell pyroptosis restricts viral replication. The mechanisms of the tripartite motif (TRIM) protein family and IFN-stimulated genes (ISGs) against viruses have been studied. The role of TRIMs and ISGs in pyroptosis remains unclear. In this study, we show that TRIM21 interacts with ISG12a in viral infection and facilitates its translocation into the mitochondria by promoting its ubiquitination, thereby causing caspase 3 activation. Gasdermin E (GSDME) is specifically cleaved by caspase 3 upon viral infection, releasing the GSDME N-terminal domain, perforating the cell membrane, and causing cell pyroptosis. Our study uncovers a new mechanism of TRIM21 and ISG12a in regulating virus-induced cell pyroptosis.

引用

页码：1987 / 1998

页数：12

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