Evidence map›Paper›PMID 39088122›Full record

ArticleInflammation2025

TRIM35 Negatively Regulates the cGAS-STING-Mediated Signaling Pathway by Attenuating K63-Linked Ubiquitination of STING.

Jikai Zhang, Yuhao Wu, Yiwen Wang, Jing Wang, Yinlin Ye, Hang Yin, Ningye Sun, Baoying Qin, Nan Sun

Abstract read
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In one paragraph

Article in Inflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Jikai ZhangXuzhou Medical University, Xuzhou, China.
Yuhao WuXuzhou Medical University, Xuzhou, China.
Yiwen WangXuzhou Medical University, Xuzhou, China.
Jing WangCenter of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Yinlin YeXuzhou Medical University, Xuzhou, China.
Hang YinXuzhou Medical University, Xuzhou, China.
Ningye SunXuzhou Medical University, Xuzhou, China.
Baoying QinXuzhou Medical University, Xuzhou, China.
Nan SunXuzhou Medical University, Xuzhou, China. sunnan312@xzhmu.edu.cn.

Funding

Jiangsu Training Program of Innovation and Entrepreneurship for Undergraduates 202210313019ZJiangsu Training Program of Innovation and Entrepreneurship for Undergraduates 202310313044ZNational Natural Science Foundation of China 32200124Natural Science Foundation of Jiangsu Province BK20210901
6 · The paper itself

Abstract

The cGAS-STING-mediated antiviral response plays an important role in the defense against DNA virus infection. Tripartite motif protein 35 (TRIM35), an E3 ubiquitin ligase, was identified as a positive regulator of RLR-mediated antiviral signaling in our previous study, but the effect of TRIM35 on the cGAS-STING signaling pathway has not been elucidated. Herein, we showed that TRIM35 negatively regulates the cGAS-STING signaling pathway by directly targeting STING. TRIM35 overexpression significantly inhibited the cGAMP-triggered phosphorylation of TBK1 and IRF3, attenuating IFN-β expression and the downstream antiviral response. Mechanistically, TRIM35 colocalized and directly interacted with STING in the cytoplasm. TRM35 removed K63-linked ubiquitin from STING through the C36 and C44 sites in the RING domain, which impaired the interaction of STING with TBK1 or IKKε. In addition, we demonstrated that the RING domain is a key region for the antiviral effects of TIRM35. These results collectively indicate that TRIM35 negatively regulates type I interferon (IFN-I) production by targeting and deubiquitinating STING. TRIM35 may be a potential therapeutic target for controlling viral infection.

Indexed as

Membrane ProteinsNucleotidyltransferasesSignal TransductionUbiquitin-Protein LigasesAnimalsCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseHEK293 CellsHumansMiceProtein Serine-Threonine KinasesSTING ProteinTripartite Motif ProteinsUbiquitinationcGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseMembrane ProteinsNucleotidyltransferasesProtein Serine-Threonine KinasesSTING1 protein, humanSTING ProteinTBK1 protein, humanTripartite Motif ProteinsUbiquitin-Protein LigasesAntiviral responsecGAS-STING signalingSTINGTRIM35Ubiquitination

Identifiers

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.