| First Author | Yang M | Year | 2015 |
| Journal | Nat Immunol | Volume | 16 |
| Issue | 12 | Pages | 1253-62 |
| PubMed ID | 26390156 | Mgi Jnum | J:233782 |
| Mgi Id | MGI:5788055 | Doi | 10.1038/ni.3258 |
| Citation | Yang M, et al. (2015) K33-linked polyubiquitination of Zap70 by Nrdp1 controls CD8(+) T cell activation. Nat Immunol 16(12):1253-62 |
| abstractText | The key molecular mechanisms that control signaling via T cell antigen receptors (TCRs) remain to be fully elucidated. Here we found that Nrdp1, a ring finger-type E3 ligase, mediated Lys33 (K33)-linked polyubiquitination of the signaling kinase Zap70 and promoted the dephosphorylation of Zap70 by the acidic phosphatase-like proteins Sts1 and Sts2 and thereby terminated early TCR signaling in CD8(+) T cells. Nrdp1 deficiency significantly promoted the activation of naive CD8(+) T cells but not that of naive CD4(+) T cells after engagement of the TCR. Nrdp1 interacted with Zap70 and with Sts1 and Sts2 and connected K33 linkage of Zap70 to Sts1- and Sts2-mediated dephosphorylation. Our study suggests that Nrdp1 terminates early TCR signaling by inactivating Zap70 and provides new mechanistic insights into the non-proteolytic regulation of TCR signaling by E3 ligases. |
