Abstract |
Stimulator of interferon genes ( STING) is critical for cytosolic DNA-triggered innate immunity. STING is modified by several types of polyubiquitin chains. Here, we report that the deubiquitinase CYLD sustains STING signaling by stabilizing the STING protein. CYLD deficiency promoted the K48-linked polyubiquitination and degradation of STING, attenuating the induction of IRF3-responsive genes after HSV-1 infection or the transfection of DNA ligands. Additionally, CYLD knockout mice were more susceptible to HSV-1 infection than their wild-type (WT) littermates. Mechanistically, STING translocated from the ER to the Golgi upon HSV-1 stimulation; CYLD partially accumulated with STING and interacted selectively with K48-linked polyubiquitin chains on STING, specifically removing the K48-linked polyubiquitin chains from STING and ultimately boosting the innate antiviral response. Our study reveals that CYLD is a novel checkpoint in the cGAS- STING signaling pathway and sheds new light on the dynamic regulation of STING activity by ubiquitination.
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Authors | Lele Zhang, Ning Wei, Ye Cui, Ze Hong, Xing Liu, Qiang Wang, Senlin Li, Heng Liu, Huansha Yu, Yanni Cai, Quanyi Wang, Juanjuan Zhu, Wei Meng, Zhengjun Chen, Chen Wang |
Journal | PLoS pathogens
(PLoS Pathog)
Vol. 14
Issue 11
Pg. e1007435
(11 2018)
ISSN: 1553-7374 [Electronic] United States |
PMID | 30388174
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antiviral Agents
- Membrane Proteins
- STING1 protein, human
- Sting1 protein, mouse
- Polyubiquitin
- CYLD protein, human
- CYLD protein, mouse
- Deubiquitinating Enzyme CYLD
- Cysteine Endopeptidases
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Topics |
- Animals
- Antiviral Agents
(metabolism)
- Cysteine Endopeptidases
(metabolism)
- Deubiquitinating Enzyme CYLD
(metabolism)
- Golgi Apparatus
(metabolism)
- HEK293 Cells
- HeLa Cells
- Herpesvirus 1, Human
(metabolism)
- Humans
- Immunity, Innate
- Membrane Proteins
(metabolism)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Polyubiquitin
(genetics)
- Signal Transduction
- Ubiquitination
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