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TRIM14 Inhibits cGAS Degradation Mediated by Selective Autophagy Receptor p62 to Promote Innate Immune Responses.
- Source :
-
Molecular Cell . Oct2016, Vol. 64 Issue 1, p105-119. 15p. - Publication Year :
- 2016
-
Abstract
- Summary 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 64
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 118523045
- Full Text :
- https://doi.org/10.1016/j.molcel.2016.08.025