Evidence map›Paper›PMID 33608556›Full record

ArticleNature communications2021

E3 ligase Nedd4l promotes antiviral innate immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3.

Peng Gao, Xianwei Ma, Ming Yuan, Yulan Yi, Guoke Liu, Mingyue Wen, Wei Jiang, Ruihua Ji, Lingxi Zhu, Zhen Tang and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
6.4field-weighted citation impact, top 2% of its field
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

68 citing papers in PubMed, 107 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. N6-methyladenosine modification of FZR1 mRNA positively regulates antiviral innate immunity by targeting the MAVS-TRAF3/6 axis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  13. Review
  14. Article
  15. SMURF2 inhibits autophagic control ofbioRxiv : the preprint server for biology · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. The Molecular Toolbox for Linkage Type-Specific Analysis of Ubiquitin Signaling.Chembiochem : a European journal of chemical biology · 2025
    Review

8 more citing papers are in PubMed but not listed here.

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

18 authors at 4 institutions in 1 country.

Peng Gao *Clinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0001-5358-6402
Xianwei Ma *Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, China.ORCID 0000-0002-7023-8204
Ming Yuan *Immunology Department & National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0001-7635-3409
Yulan Yi *Clinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0002-3488-5404
Guoke LiuClinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0003-4623-6433
Mingyue WenImmunology Department & National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0001-9372-2579
Wei JiangClinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.
Ruihua JiDepartment of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.ORCID 0000-0002-0562-9989
Lingxi ZhuClinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0003-0659-9424
Zhen TangClinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0002-6250-3768
Qingzhuo YuClinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0003-0844-3482
Jing XuClinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0003-2148-2638
Rui YangDepartment of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
Sheng XiaDepartment of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.ORCID 0000-0002-0663-6988
Mingjin YangImmunology Department & National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, 200433, China.ORCID 0000-0003-2350-1054
Jianping PanDepartment of Clinical Medicine, Zhejiang University City College School of Medicine, Hangzhou, 310015, China.ORCID 0000-0001-9636-1561
Hongbin YuanDepartment of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. jfjczyy@163.com.ORCID 0000-0001-8468-4005
Huazhang AnClinical Cancer Institute, Center for Translational Medicine, Second Military Medical University, Shanghai, 200433, China. anhz@immunol.org.ORCID 0000-0001-8120-9145
Second Military Medical University · CNJiangsu University · CNShanghai Public Health Clinical Center · CNZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ubiquitination is one of the most prevalent protein posttranslational modifications. Here, we show that E3 ligase Nedd4l positively regulates antiviral immunity by catalyzing K29-linked cysteine ubiquitination of TRAF3. Deficiency of Nedd4l significantly impairs type I interferon and proinflammatory cytokine production induced by virus infection both in vitro and in vivo. Nedd4l deficiency inhibits virus-induced ubiquitination of TRAF3, the binding between TRAF3 and TBK1, and subsequent phosphorylation of TBK1 and IRF3. Nedd4l directly interacts with TRAF3 and catalyzes K29-linked ubiquitination of Cys56 and Cys124, two cysteines that constitute zinc fingers, resulting in enhanced association between TRAF3 and E3 ligases, cIAP1/2 and HECTD3, and also increased K48/K63-linked ubiquitination of TRAF3. Mutation of Cys56 and Cys124 diminishes Nedd4l-catalyzed K29-linked ubiquitination, but enhances association between TRAF3 and the E3 ligases, supporting Nedd4l promotes type I interferon production in response to virus by catalyzing ubiquitination of the cysteines in TRAF3.

Indexed as

UbiquitinationAnimalsBaculoviral IAP Repeat-Containing 3 ProteinCatalysisCysteineFemaleHEK293 CellsHumansImmunity, InnateInhibitor of Apoptosis ProteinsInterferon Regulatory Factor-3Interferon Type IMiceMice, Inbred C57BLMice, KnockoutNedd4 Ubiquitin Protein LigasesBaculoviral IAP Repeat-Containing 3 ProteinCysteineHECTd3 protein, mouseInhibitor of Apoptosis ProteinsInterferon Regulatory Factor-3Interferon Type IIrf3 protein, mouseNedd4l protein, mouseNedd4 Ubiquitin Protein LigasesProtein Serine-Threonine KinasesTbk1 protein, mouseTNF Receptor-Associated Factor 3Ubiquitin-Protein Ligases

Identifiers

PMID33608556
PMCPMC7895832
OpenAlexW3130035319

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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 OpenQuestion graph.