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  • Title: TRIM14 Inhibits cGAS Degradation Mediated by Selective Autophagy Receptor p62 to Promote Innate Immune Responses.
    Author: Chen M, Meng Q, Qin Y, Liang P, Tan P, He L, Zhou Y, Chen Y, Huang J, Wang RF, Cui J.
    Journal: Mol Cell; 2016 Oct 06; 64(1):105-119. PubMed ID: 27666593.
    Abstract:
    Cyclic GMP-AMP synthase (cGAS) is an essential DNA virus sensor that triggers type I interferon (IFN) signaling by producing cGAMP to initiate antiviral immunity. However, post-translational regulation of cGAS remains largely unknown. We report that K48-linked ubiquitination of cGAS is a recognition signal for p62-depdendent selective autophagic degradation. The induction of TRIM14 by type I IFN accelerates cGAS stabilization by recruiting USP14 to cleave the ubiquitin chains of cGAS at lysine (K) 414. Knockout of TRIM14 impairs herpes simplex virus type 1 (HSV-1)-triggered antiviral responses in a cGAS-dependent manner. Due to impaired type I IFN production, Trim14-/- mice are highly susceptible to lethal HSV-1 infection. Taken together, our findings reveal a positive feedback loop of cGAS signaling generated by TRIM14-USP14 and provide insights into the crosstalk between autophagy and type I IFN signaling in innate immunity.
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