Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus

Song, Soonhwa; Lee, Jae Jin; Kim, Hee Jung; Lee, Yoo‐Hyun; Chang, Jun; Lee, Kong Joo

doi:10.1128/mcb.00744-15

Cited by 20 publications

(22 citation statements)

References 44 publications

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“…Pathway enrichment analysis of YTHDF2 in LGG by GESA found that the genes correlated with YTHDF2 were more significantly enriched in cell cycle, TCA cycle, DNA replication, and the FAS signaling pathway. Interestingly, the most significant gene positively associated with YTHDF2, FAF1, can regulate antiviral immunity ([ 80 , 81 ]). Moreover, notch family genes (the pathway found in the enrichment analysis) were prognostic biomarkers and correlated with immune infiltrates in gastric cancer ([ 82 ]).…”

Section: Discussionmentioning

confidence: 99%

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

Lin

Wang²,

Yang³

et al. 2020

Aging

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Immunotherapy is an effective treatment for many cancer types. However, YTHDF2 effects on the prognosis of different tumors and correlation with tumor immune infiltration are unclear. Here, we analyzed The Cancer Genome Atlas and Gene Expression Omnibus data obtained through various web-based platforms. The analyses showed that YTHDF2 expression and associated prognoses may depend on cancer type. High YTHDF2 expression was associated with poor overall survival in lower-grade glioma (LGG). In addition, YTHDF2 expression positively correlated with expression of several immune cell markers, including PD-1, TIM-3, and CTLA-4, as well as tumor-associated macrophage gene markers, and isocitrate dehydrogenase 1 in LGG. These findings suggest that YTHDF2 is a potential prognostic biomarker that correlates with LGG tumor-infiltrating immune cells.

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Section: Discussionmentioning

confidence: 99%

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

Lin

Wang²,

Yang³

et al. 2020

Aging

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“…Therefore, it may be possible that PLK2 catalyzes the phosphorylation of the substrate responsible for IRF3 nuclear trafficking. IRF3 translocation was shown to be mediated by PTEN, Rubicon, and IPO5/ Importin-b3 (13,14,33), which may be regulated by PLK2.…”

Section: Discussionmentioning

confidence: 99%

Hu Antigen R Regulates Antiviral Innate Immune Responses through the Stabilization of mRNA for Polo-like Kinase 2

Sueyoshi

Kawasaki

Kitai

et al. 2018

The Journal of Immunology

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Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), RIG-I, and melanoma differentiation-associated gene 5 (MDA5) play a critical role in inducing antiviral innate immune responses by activating IFN regulatory factor 3 (IRF3) and NF-κB, which regulates the transcription of type I IFN and inflammatory cytokines. Antiviral innate immune responses are also regulated by posttranscriptional and translational mechanisms. In this study, we identified an RNA-binding protein HuR as a regulator for RLR signaling. Overexpression of HuR, but not of other Hu members, increased IFN-β promoter activity. HuR-deficient macrophage cells exhibited decreased expression after RLR stimulation, whereas they showed normal induction after stimulation with bacterial LPS or immunostimulatory DNA. Moreover, HuR-deficient cells displayed impaired nuclear translocation of IRF3 after RLR stimulation. In HuR-deficient cells, the mRNA expression of Polo-like kinase (PLK) 2 was markedly reduced. We found that HuR bound to the 3' untranslated region of mRNA and increased its stabilization. PLK2-deficient cells also showed reduced IRF3 nuclear translocation and mRNA expression during RLR signaling. Together, these findings suggest that HuR bolsters RLR-mediated IRF3 nuclear translocation by controlling the stability of mRNA.

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“…The majority of characterized inhibitors of IRF3 activity target IRF3 for ubiquitination and degradation, for example Forkhead box protein O1 (FOXO1) (19), RTA-associated ubiquitin ligase (RAUL) (20), and tripartite motif-containing 26 (TRIM26) (21). Fas-associated factor 1 has been shown to prevent interactions of IRF3 with importins (22), thus inhibiting nuclear trafficking in response to viral stimuli. An additional inhibitor of IRF3, cellular FLICE-like inhibitory protein (cFLIP L ) inhibits IFN-␤ transcription by binding to IRF3 and preventing its association with CBP within the nucleus (23).…”

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confidence: 99%

C6orf106 is a novel inhibitor of the interferon-regulatory factor 3–dependent innate antiviral response

Ambrose

Liu

Adams

et al. 2018

Journal of Biological Chemistry

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Host recognition of intracellular viral RNA and subsequent induction of cytokine signaling are tightly regulated at the cellular level and are a target for manipulation by viruses and therapeutics alike. Here, we characterize chromosome 6 ORF 106 (C6orf106) as an evolutionarily conserved inhibitor of the innate antiviral response. C6orf106 suppresses the synthesis of interferon (IFN)-α/β and proinflammatory tumor necrosis factor (TNF) α in response to the dsRNA mimic poly(I:C) and to Sendai virus infection. Unlike canonical inhibitors of antiviral signaling, C6orf106 blocks interferon-regulatory factor 3 (IRF3) and, to a lesser extent, NF-κB activity without modulating their activation, nuclear translocation, cellular expression, or degradation. Instead, C6orf106 interacts with IRF3 and inhibits IRF3 recruitment to type I IFN promoter sequences while also reducing the nuclear levels of the coactivator proteins p300 and CREB-binding protein (CBP). In summary, we have defined C6orf106 as a negative regulator of antiviral immunity that blocks IRF3-dependent cytokine production via a noncanonical and poorly defined mechanism. This work presents intriguing implications for antiviral immunity, autoimmune disorders, and cancer.

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Fas-Associated Factor 1 Negatively Regulates the Antiviral Immune Response by Inhibiting Translocation of Interferon Regulatory Factor 3 to the Nucleus

Cited by 20 publications

References 44 publications

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma

Hu Antigen R Regulates Antiviral Innate Immune Responses through the Stabilization of mRNA for Polo-like Kinase 2

C6orf106 is a novel inhibitor of the interferon-regulatory factor 3–dependent innate antiviral response

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