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RINCK-mediated monoubiquitination of cGAS promotes antiviral innate immune responses

Overview of attention for article published in Cell & Bioscience, May 2018
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RINCK-mediated monoubiquitination of cGAS promotes antiviral innate immune responses
Published in
Cell & Bioscience, May 2018
DOI 10.1186/s13578-018-0233-3
Pubmed ID

Zhao-Shan Liu, Zi-Yu Zhang, Hong Cai, Ming Zhao, Jie Mao, Jiang Dai, Tian Xia, Xue-Min Zhang, Tao Li


As an important danger signal, the presence of DNA in cytoplasm triggers potent immune responses. Cyclic GMP-AMP synthase (cGAS) is a recently characterized key sensor for cytoplasmic DNA. The engagement of cGAS with DNA leads to the synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which binds and activates the downstream adaptor protein STING to promote type I interferon production. Although cGAS has been shown to play a pivotal role in innate immunity, the exact regulation of cGAS activation is not fully understood. We report that an E3 ubiquitin ligase, RING finger protein that interacts with C kinase (RINCK, also known as tripartite motif protein 41, TRIM41), is critical for cGAS activation by mediating the monoubiquitination of cGAS. Using CRISPR/Cas9, we generated RINCK-deletion cells and showed that the deficiency of RINCK resulted in dampened interferon production in response to cytosolic DNA. Consistently, the RINCK-deletion cells also exhibited insufficient interferon production upon herpes simplex virus 1, a DNA virus, infection. As a result, the viral load in RINCK-deficient cells was significantly higher than that in wild-type cells. We also found that RINCK deficiency inhibited the up-stream signaling of DNA-triggered interferon production pathway, which was reflected by the phosphorylation of the TANK-binding kinase 1 and the interferon regulatory factor 3. Interestingly, we found that RINCK binds to cGAS and promotes the monoubiquitination of cGAS, thereby positively regulating the cGAS-mediated cGAMP synthesis. Our study reveals that monoubiquitination is an important regulation for cGAS activation and uncovers a critical role of RINCK in the cGAS-mediated innate immunity.

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Mendeley readers

The data shown below were compiled from readership statistics for 29 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 29 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 28%
Researcher 5 17%
Student > Bachelor 4 14%
Student > Master 3 10%
Student > Postgraduate 2 7%
Other 3 10%
Unknown 4 14%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 41%
Immunology and Microbiology 5 17%
Medicine and Dentistry 3 10%
Agricultural and Biological Sciences 2 7%
Chemistry 2 7%
Other 1 3%
Unknown 4 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 May 2018.
All research outputs
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Outputs from Cell & Bioscience
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Outputs of similar age
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Outputs of similar age from Cell & Bioscience
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Altmetric has tracked 13,793,900 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 344 research outputs from this source. They receive a mean Attention Score of 2.0. This one has gotten more attention than average, scoring higher than 51% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 272,739 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them