Ubc9Is Required for Positive Selection and Late-Stage Maturation of Thymocytes.
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 deletingUbc9gene in T cells, we have investigated the functional roles of SUMOylation in T cell development. Loss ofUbc9results 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 ofUbc9-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.
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Aibo
0000-0003-0238-9550
A
Wang
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Xiao
X
Ding
Nuclear Organization and Oncogenesis Laboratory, Department of Cell Biology and Infection, INSERM U993, Institute Pasteur, 75015 Paris, France.
Maud
M
Demarque
Southwest Hospital, Third Military Medical University, 400038 Chongqing, China.
Xindong
X
Liu
Department of Immunology and Center for Inflammation and Cancer, The University of Texas MD Anderson Cancer Center, Houston, TX 77054; and.
Deng
D
Pan
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Huawei
0000-0003-4017-6572
H
Xin
College of Life Sciences, Wuhan University, Wuhan 430072, China.
Bo
B
Zhong
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Xiaohu
X
Wang
Nuclear Organization and Oncogenesis Laboratory, Department of Cell Biology and Infection, INSERM U993, Institute Pasteur, 75015 Paris, France.
Anne
A
Dejean
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China.
Wei
W
Jin
Institute for Immunology and School of Medicine, Tsinghua University, Beijing 100084, China; chendong@tsinghua.edu.cn.
Chen
C
Dong
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002470:Cell Survival / Q000235:genetics; D060966:Clonal Selection, Antigen-Mediated; D015851:Interleukin-7 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D050778:NFATC Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D058207:Sumoylation / Q000235:genetics; D060168:Thymocytes / Q000502:physiology*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D015851:Interleukin-7; D050778:NFATC Transcription Factors; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9