| First Author | Zhang MX | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 8 | Pages | 2397-2406 |
| PubMed ID | 30814308 | Mgi Jnum | J:274572 |
| Mgi Id | MGI:6287924 | Doi | 10.4049/jimmunol.1801447 |
| Citation | Zhang MX, et al. (2019) USP20 Promotes Cellular Antiviral Responses via Deconjugating K48-Linked Ubiquitination of MITA. J Immunol 202(8):2397-2406 |
| abstractText | Mediator of IRF3 activation ([MITA] also known as STING) is a direct sensor of cyclic dinucleotide and critically mediates cytoplasmic DNA--triggered innate immune signaling. The activity of MITA is extensively regulated by ubiquitination and deubiquitination. In this study, we report that USP20 interacts with and removes K48-linked ubiquitin chains from MITA after HSV-1 infection, thereby stabilizing MITA and promoting cellular antiviral responses. Deletion of USP20 accelerates HSV-1-induced degradation of MITA and impairs phosphorylation of IRF3 and IkappaBalpha as well as subsequent induction of type I IFNs and proinflammatory cytokines after HSV-1 infection or cytoplasmic DNA challenge. Consistently, Usp20 (-/-) mice produce decreased type I IFNs and proinflammatory cytokines, exhibit increased susceptibility to lethal HSV-1 infection, and aggravated HSV-1 replication compared with Usp20 (+/+) mice. In addition, complement of MITA into Usp20 (-/-) cells fully restores HSV-1-triggered signaling and inhibits HSV-1 infection. These findings suggest a crucial role of USP20 in maintaining the stability of MITA and promoting innate antiviral signaling. |
