Cell Death and Differentiation · 2022 · 49 citations · 39 references
Life SciencesImmunologyMolecular BiologyInnate ImmunityMolecular ImmunologyMolecular VirologyAntiviral ImmunityImmune RegulationImmune Signaling PathwaysInnate Immune ResponseInnate Immune Signaling PathwaysViral Immune EvasionAntiviral Innate Immune SignalingAntiviral Innate SignalingHost Antiviral ResponseInnate Immune HomeostasisMechanistic ExplanationProteasomal TurnoverViral Evasion MechanismsViral Evasion Of Host Immunity
The precise regulation of STING homeostasis is essential for its antiviral function. Post-translational modification, especially ubiquitination, is important for the regulation of STING homeostasis. Previous studies have focused on how STING is degraded, but little is known about its maintenance. Here, we show that UFM1 specific ligase UFL1 promotes innate immune response by maintaining STING expression independent of UFMylation. Mechanistically, UFL1 inhibits TRIM29 to interact with STING, thereby reducing its ubiquitination at K338/K347/K370 and subsequent proteasomal degradation. DNA virus infection reduces the UFL1 expression, which may promote STING degradation and facilitate viral expansion. Our study identifies UFL1 as a crucial regulator for the maintenance of STING stability and antiviral function, and provides novel insights into the mechanistic explanation for the immunological escape of DNA virus.
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Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
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cGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING
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