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Publication : <i>Ubc9</i> Is Required for Positive Selection and Late-Stage Maturation of Thymocytes.

First Author  Wang A Year  2017
Journal  J Immunol Volume  198
Issue  9 Pages  3461-3470
PubMed ID  28314856 Mgi Jnum  J:247677
Mgi Id  MGI:5926013 Doi  10.4049/jimmunol.1600980
Citation  Wang A, et al. (2017) Ubc9 Is Required for Positive Selection and Late-Stage Maturation of Thymocytes. J Immunol 198(9):3461-3470
abstractText  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.
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