Deubiquitinase OTULIN dampens RIG-I-dependent antiviral signaling by removing linear ubiquitination from TRAF6 - PubMed
14 hours ago
- #TRAF6
- #OTULIN
- #antiviral signaling
- OTULIN negatively regulates RIG-I-dependent type I IFN signaling by removing linear ubiquitination from TRAF6.
- Overexpression of OTULIN suppresses NF-κB and IFNβ activation, downstream gene expression, and IFN-I production, facilitating viral replication.
- Knockout of OTULIN enhances antiviral signaling and restricts viral replication, which is reversed by reintroducing OTULIN.
- RNA virus infection induces linear ubiquitination of TRAF6 at specific lysine residues (K104, K142, K371), promoted by LUBAC and antagonized by OTULIN.
- Linear ubiquitination of TRAF6 facilitates its K63-linked ubiquitination and strengthens its association with MAVS, amplifying the antiviral response.
- Otulin+/- mice show enhanced antiviral immunity and more efficient viral clearance compared to wild-type mice.
- The study highlights the balance between linear ubiquitination and deubiquitination in antiviral innate immunity and immune homeostasis.