| First Author | Zhong B | Year | 2012 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 11 | Pages | 1110-7 |
| PubMed ID | 23042150 | Mgi Jnum | J:188557 |
| Mgi Id | MGI:5441108 | Doi | 10.1038/ni.2427 |
| Citation | Zhong B, et al. (2012) Negative regulation of IL-17-mediated signaling and inflammation by the ubiquitin-specific protease USP25. Nat Immunol 13(11):1110-7 |
| abstractText | Interleukin 17 (IL-17) is important in infection and autoimmunity; how it signals remains poorly understood. In this study, we identified the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation. Overexpression of USP25 inhibited IL-17-triggered signaling, whereas USP25 deficiency resulted in more phosphorylation of the inhibitor IkappaBalpha and kinase Jnk and higher expression of chemokines and cytokines, as well as a prolonged half-life for chemokine CXCL1-encoding mRNA after treatment with IL-17. Consistent with that, Usp25(-/-) mice showed greater sensitivity to IL-17-dependent inflammation and autoimmunity in vivo. Mechanistically, stimulation with IL-17 induced the association of USP25 with the adaptors TRAF5 and TRAF6, and USP25 induced removal of Lys63-linked ubiquitination in TRAF5 and TRAF6 mediated by the adaptor Act1. Thus, our results demonstrate that USP25 is a deubiquitinating enzyme (DUB) that negatively regulates IL-17-triggered signaling. |
