K63-linked polyubiquitination of LGP2 by Riplet regulates RIG-I-dependent innate immune response.

EMBO Rep

Department of Immunology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Published: February 2023

Type I interferons (IFNs) exhibit strong antiviral activity and induce the expression of antiviral proteins. Since excessive expression of type I IFNs is harmful to the host, their expression should be turned off at the appropriate time. In this study, we find that post-translational modification of LGP2, a member of the RIG-I-like receptor family, modulates antiviral innate immune responses. The LGP2 protein undergoes K63-linked polyubiquitination in response to cytoplasmic double-stranded RNAs or viral infection. Our mass spectrometry analysis reveals the K residues ubiquitinated by the Riplet ubiquitin ligase. LGP2 ubiquitination occurs with a delay compared to RIG-I ubiquitination. Interestingly, ubiquitination-defective LGP2 mutations increase the expression of type I IFN at a late phase, whereas the mutant proteins attenuate other antiviral proteins, such as SP100, PML, and ANKRD1. Our data indicate that delayed polyubiquitination of LGP2 fine-tunes RIG-I-dependent antiviral innate immune responses at a late phase of viral infection.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9900346PMC
http://dx.doi.org/10.15252/embr.202254844DOI Listing

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