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

Aibo Wang (1) , Xiao Ding (1) , Maud Demarque (2) , Xindong Liu (3) , Deng Pan (4) , Huawei Xin (1) , Bo Zhong (5) , Xiaohu Wang (1) , Anne Dejean (2) , Wei Jin (1) , Chen Dong (1)

1 THU - Tsinghua University [Beijing]
2 Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis
3 Third Military Medical University
4 The University of Texas M.D. Anderson Cancer Center [Houston]
5 Wuhan University [China]

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.

Domains: Life Sciences [q-bio]

Aibo Wang, Xiao Ding, Maud Demarque, Xindong Liu, Deng Pan, et al.. Ubc9 Is Required for Positive Selection and Late-Stage Maturation of Thymocytes. Journal of Immunology, 2017, 198 (9), pp.3461-3470. ⟨10.4049/jimmunol.1600980⟩. ⟨pasteur-03234899⟩