| First Author | Hu H | Year | 2016 |
| Journal | J Exp Med | Volume | 213 |
| Issue | 3 | Pages | 399-414 |
| PubMed ID | 26903241 | Mgi Jnum | J:232930 |
| Mgi Id | MGI:5780482 | Doi | 10.1084/jem.20151426 |
| Citation | Hu H, et al. (2016) Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination. J Exp Med 213(3):399-414 |
| abstractText | Signal transduction from the T cell receptor (TCR) is crucial for T cell-mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitating TCR signaling. Upon TCR ligation, Otud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal signaling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell-mediated autoimmune and inflammatory responses. Otud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phosphatases Sts1 and Sts2. These findings establish Otud7b as a positive regulator of TCR-proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating Zap70 function. |
