The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
The E3 Ubiquitin Ligase Ro52 Negatively Regulates IFN-β Production Post-Pathogen Recognition by Polyubiquitin-Mediated Degradation of IRF3
Open accessAbstract
Induction of type I IFNs is a fundamental cellular response to both viral and bacterial infection. The role of the transcription factor IRF3 is well established in driving this process. However, equally as important are cellular mechanisms for turning off type I IFN production to limit this response. In this respect, IRF3 has previously been shown to be targeted for ubiquitin-mediated degradation postviral detection to turn off the IFN-β response. In this study, we provide evidence that the E3 ligase Ro52 (TRIM21) targets IRF3 for degradation post-pathogen recognition receptor activation. We demonstrate that Ro52 interacts with IRF3 via its C-terminal SPRY domain, resulting in the polyubiquitination and proteasomal degradation of the transcription factor. Ro52-mediated IRF3 degradation significantly inhibits IFN-β promoter activity, an effect that is reversed in the presence of the proteasomal inhibitor MG132. Specific targeting of Ro52 using short hairpin RNA rescues IRF3 degradation following polyI:C-stimulation of HEK293T cells, with a subsequent increase in IFN-β production. Additionally, shRNA targeting of murine Ro52 enhances the production of the IRF3-dependent chemokine RANTES following Sendai virus infection of murine fibroblasts. Collectively, this demonstrates a novel role for Ro52 in turning off and thus limiting IRF3-dependent type I IFN production by targeting the transcription factor for polyubiquitination and subsequent proteasomal degradation.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Several TRIM proteins regulate production and action of IFN-β during innate immune response.”
From TRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation (2015) · cites this paper as [36]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
IKKε and TBK1 are essential components of the IRF3 signaling pathway
Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M., & Maniatis, T. (2003) · Nature Immunology · doi:10.1038/ni921 · Cited by 2,680
Self-citationInnate immune recognition of viral infection
Kawai, T., & Akira, S. (2006) · Nature Immunology · doi:10.1038/ni1303 · Cited by 1,899
Triggering the Interferon Antiviral Response Through an IKK-Related Pathway
Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G., Lin, R., & Hiscott, J. B. (2003) · Science · doi:10.1126/science.1081315 · Cited by 1,685
TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity
Gack, M. U., Shin, Y. C., Joo, C.-H., Urano, T., Liang, C., Sun, L., Takeuchi, O., Akira, S., Chen, Z. J., Inoue, S., et al. (2007) · Nature · doi:10.1038/nature05732 · Cited by 1,683
Sato, M., Suemori, H., Hata, N., Asagiri, M., Ogasawara, K., Nakao, K., Nakaya, T., Katsuki, M., Noguchi, S., Tanaka, N., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00053-4 · Cited by 1,342
The International Consortium for Systemic Lupus Erythematosus Genetics (SLEGEN), Harley, J. B., Alarcón-Riquelme, M. E., Criswell, L. A., Jacob, C. O., Kimberly, R. P., Moser, K. L., Tsao, B. P., Vyse, T. J., & Langefeld, C. D. (2008) · Nature Genetics · doi:10.1038/ng.81 · Cited by 1,309
Kawai, T., Takeuchi, O., Fujita, T., Inoue, J., Mühlradt, P. F., Sato, S., Hoshino, K., & Akira, S. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.10.5887 · Cited by 1,115
Kawai, T., Sato, S., Ishii, K. J., Coban, C., Hemmi, H., Yamamoto, M., Terai, K., Matsuda, M., Inoue, J., Uematsu, S., et al. (2004) · Nature Immunology · doi:10.1038/ni1118 · Cited by 1,058
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–310 of 310
TRIM25 promotes antiviral innate immune response by stabilizing IRF7 and its nuclear translocation
Wu, Z., Cui, Y., He, Y., Wang, T., Hu, T., Wang, M., Jia, R., Zhu, D., Liu, M., Zhao, X., et al. (2026) · mBio · doi:10.1128/mbio.00470-26
Inhibition de la transcription inverse du VIH-1 par la protéine Daxx
Maillet, S. (2020) · theses.fr (ABES) · doi:10.70675/54d97cdczd6ffz4611zae08zdf67cd500efd
EBV (LMP1) enhances cisplatin resistance by enhancing degradation of interferon regulatory factor 3
Li, Y., Liu, N., Yang, C., He, S., Luo, C., Wang, L., Tang, M., Luo, X., Cao, Y., Li, S., et al. (2026) · Cell Communication and Signaling · doi:10.1186/s12964-026-02934-9
TRIM21 inhibited PRV infection and downregulated IFN-α, IL-6, and TNF-α during the infection
Zhang, G., Dong, M., Li, P., Huang, J., Yin, R., Lv, X., Yang, L., & Ren, L. (2026) · Microbial Pathogenesis · doi:10.1016/j.micpath.2026.108610
OLFML3 negatively regulates RIG-I signaling in RNA virus infection
Gu, Q., Mei, H., Yu, Q., Yu, P., Zhang, J., Hu, P., Qu, J. M., & Liu, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1810852
Tan, K., Chen, Y., Zhou, C., Guo, Y., Chen, Y., & Sun, B. (2026) · Clinica Chimica Acta · doi:10.1016/j.cca.2026.121296
Unraveling the Multifaceted Role of TRIM21 in Virus-Triggered Innate Immunity and Diseases
Lan, S., Wang, Y., Fu, Y., Yang, S., Shen, Q., Wang, X., Zhang, W., Wang, D., & Ji, L. (2026) · Biomolecules · doi:10.3390/biom16091237
TRIM28 contributes to epidermal homeostasis and is associated with altered p53 regulation
Beer, L., Kühtreiber, H., Auer, L., Wagner, T., Golabi, B., Röder, S. A., Salek, M., & Mildner, M. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1903169
Enrichment of the TRIM21-IgG complex in placental villi during HIV-1 infection
Campo, B. N., de Sousa, E. S. A., Pereira, N. Z., Pietrobon, A. J., Milanez, H. M. B. P. M., Sotto, M. N., Mattos, G. D., Simões, G. B., Sousa, D. P., Naresse, M. D. M., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1922263
Yu, M., Jo, D., Hwang, Y., & Han, K. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27209042
Metadata
- Authors
- Higgs, R., Gabhann, J. N., Larbi, N. B., Breen, E. P., Fitzgerald, K. A., & Jefferies, C. A.
- Affiliations
- Royal College of Surgeons in Ireland (IE)
- University of Massachusetts Chan Medical School (US)
- Corresponding author
- Higgs, Rowan
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-08-01
- Volume
- 181
- Issue
- 3
- Pages
- 1780-1786
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC2824853
- OpenAlex
- W2129691636
- Cited by
- 310
- References
- 47
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 10 · 2023: 21 · 2022: 17 · 2021: 25 · 2020: 14 · 2019: 17 · 2018: 20 · 2017: 14 · 2016: 13 · 2015: 17 · 2014: 18 · 2013: 24 · 2012: 19
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
- Funders
- Health Research Board
- Science Foundation Ireland
- National Institutes of Health (AI067497, AI067497 to K.A.F)
- National Institute of Allergy and Infectious Diseases (R01AI067497, R37AI067497, AI-067497, R56AI067497)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- Ro52, TRIM21, IRF3, type I interferon, interferon-beta, E3 ubiquitin ligase, polyubiquitination, proteasomal degradation, SPRY domain, interferon regulation, RANTES, Sendai virus, viral infection, chemokine production
- MeSH terms
- DEAD Box Protein 58, SS-A Antigen, Cell Line, Humans, Promoter Regions, Genetic, Protein Binding, Receptors, Immunologic, Ribonucleoproteins, Signal Transduction, Interferon-beta, Polyubiquitin, Ubiquitin-Protein Ligases, Interferon Regulatory Factor-3, Toll-Like Receptor 3, Toll-Like Receptor 4, DEAD-box RNA Helicases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
