Abstract
Protein ubiquitination plays an essential role in the regulation of retinoic acid-inducible gene I (RIG-I) activation and the antiviral immune response. However, the function of the opposite process of deubiquitination in RIG-I activation remains elusive. In this study, we have identified the deubiquitinating enzyme ubiquitin-specific protease 4 (USP4) as a new regulator for RIG-I activation through deubiquitination and stabilization of RIG-I. USP4 expression was attenuated after virus-induced RIG-I activation. Overexpression of USP4 significantly enhanced RIG-I protein expression and RIG-I-triggered beta interferon (IFN-β) signaling and, at the same time, inhibited vesicular stomatitis virus (VSV) replication. Small interfering RNA (siRNA) knockdown of USP4 expression had an opposite effect. Furthermore, USP4 was found to interact with RIG-I and remove K48-linked polyubiquitination chains from RIG-I. Therefore, we identified USP4 as a new positive regulator for RIG-I that acts through deubiquitinating K48-linked ubiquitin chains and stabilizing RIG-I.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.