Ubc9 Is Required for Positive Selection and Late-Stage Maturation of Thymocytes

被引：20

作者：

Wang, Aibo ^{[1
,2
,8
]}

Ding, Xiao ^{[1
,2
]}

Demarque, Maud ^{[3
,9
]}

Liu, Xindong ^{[4
]}

Pang, Deng ^{[5
,6
]}

Xin, Huawei ^{[1
,2
]}

Zhong, Bo ^{[7
]}

Wang, Xiaohu ^{[1
,2
]}

Dejean, Anne ^{[3
]}

Jin, Wei ^{[1
,2
]}

Dong, Chen ^{[1
,2
]}

机构：

[1] Tsinghua Univ, Inst Immunol, 30 Shuangqing Rd, Beijing 100084, Peoples R China

[2] Tsinghua Univ, Sch Med, 30 Shuangqing Rd, Beijing 100084, Peoples R China

[3] Inst Pasteur, INSERM U993, Dept Cell Biol & Infect, Nucl Org & Oncogenesis Lab, F-75015 Paris, France

[4] Third Mil Med Univ, Southwest Hosp, Chongqing 400038, Peoples R China

[5] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77054 USA

[6] Univ Texas MD Anderson Canc Ctr, Ctr Inflammat & Canc, Houston, TX 77054 USA

[7] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China

[8] Xiaoping Ind Pk, Guangzhou, Guangdong, Peoples R China

[9] Univ Geneva, Natl Ctr Competence Res Frontiers Genet, Dept Mol Biol, Geneva, Switzerland

来源：

JOURNAL OF IMMUNOLOGY | 2017年 / 198卷 / 09期

基金：

中国国家自然科学基金;

关键词：

T-CELL DEVELOPMENT; NF-KAPPA-B; SIGNAL-TRANSDUCTION; NEGATIVE SELECTION; CD4+8+ THYMOCYTES; THYMIC SELECTION; TRANSGENIC MICE; SUMO PATHWAY; SUMOYLATION; EXPRESSION;

D O I：

10.4049/jimmunol.1600980

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

SUMOylation is an important posttranslational modification that regulates protein function in diverse biological processes. However, its role in early T cell development has not been genetically studied. UBC9 is the only E2 enzyme for all SUMOylation. In this study, by selectively deleting Ubc9 gene in T cells, we have investigated the functional roles of SUMOylation in T cell development. Loss of Ubc9 results in a significant reduction of CD4 and CD8 single-positive lymphocytes in both thymus and periphery. Ubc9-deficient cells exhibit defective late-stage maturation post the initial positive selection with increased apoptosis and impaired proliferation, among which attenuated IL-7 signaling was correlated with the decreased survival of Ubc9-deficent CD8 single-positive cells. Furthermore, NFAT nuclear retention induced by TCR signals was regulated by SUMOylation during thymocytes development. Our study thus reveals a novel posttranslational mechanism underlying T cell development.

引用

页码：3461 / 3470

页数：10

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