USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA.

ABSTRACT: STING (also known as MITA) mediates the innate antiviral signaling and ubiquitination of STING is key to its function. However, the deubiquitination process of STING is unclear. Here we report that USP18 recruits USP20 to deconjugate K48-linked ubiquitination chains from STING and promotes the stability of STING and the expression of type I IFNs and proinflammatory cytokines after DNA virus infection. USP18 deficiency or knockdown of USP20 resulted in enhanced K48-linked ubiquitination and accelerated degradation of STING, and impaired activation of IRF3 and NF-κB as well as induction of downstream genes after infection with DNA virus HSV-1 or transfection of various DNA ligands. In addition, Usp18^-/- mice were more susceptible to HSV-1 infection compared with the wild-type litt

SUBMITTER: Zhang M 

PROVIDER: S-EPMC5143414 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature