ArticleMolecular cell2014
Innate antiviral host defense attenuates TGF-β function through IRF3-mediated suppression of Smad signaling.
Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 83 citations in OpenAlex.
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- Oncogenic EGFR rewires STING-TBK1 signalosomes to license DNA damage tolerance in NSCLC.The EMBO journal · 2026Article
- Non-transcriptional activity of IRF3 promotes liver fibrosis and stress granule assembly via a dsRNA-TLR3-dependent pathway in hepatic stellate cells.Hepatology (Baltimore, Md.) · 2026Article
- Rationally Designed Dual Kinase Inhibitors for Management of Obstructive Sleep Apnea-A Computational Study.Biomedicines · 2026Article
- Double stranded RNA sensing is silenced during early embryonic development.Nature communications · 2025Article
- SMAD3 and p300 complex scaffolding by long non-coding RNA LIMD1-AS1 promotes TGF-β-induced breast cancer cell plasticity.Nucleic acids research · 2025Article
- Premature cell senescence promotes vascular smooth muscle cell phenotypic modulation and resistance to re-differentiation.Cardiovascular research · 2025Article
- Phosphorylated IRF3 promotes GSDME-mediated pyroptosis through RIPK1/FADD/caspase-8 complex formation during mitotic arrest in ovarian cancer.Cell communication and signaling : CCS · 2025Article
- Article
- Signature Construction Associated with Tumor-Infiltrating Macrophages Identifies IRF8 as a Novel Biomarker for Immunotherapy in Advanced Gastric Cancer.International journal of molecular sciences · 2025Article
- The innate immune axis drives aortic dissection pathogenesis through inflammation and presents novel therapeutic targets.Frontiers in immunology · 2025Review
- MiR-23b-3p ameliorates sepsis-induced acute lung injury by inhibiting SMAD3-mediated endothelial-mesenchymal transition.Burns & trauma · 2025Article
- What goes up must come down: dynamics of type 1 interferon signaling across the lifespan.Frontiers in immunology · 2025Review
- TBK1-Zyxin signaling controls tumor-associated macrophage recruitment to mitigate antitumor immunity.The EMBO journal · 2024Article
- IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis.Science advances · 2024Article
- TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective.Nature reviews. Immunology · 2023Review
- Intrinsic RIG-I restrains STAT5 activation to modulate antitumor activity of CD8+ T cells.The Journal of clinical investigation · 2023Article
- A non-canonical cGAS-STING-PERK pathway facilitates the translational program critical for senescence and organ fibrosis.Nature cell biology · 2022Article
- PolyI:C attenuates transforming growth factor-β signaling to induce cytostasis of surrounding cells by secreted factors in triple-negative breast cancer.Cancer science · 2022Article
- Comparative Investigation of Gene Regulatory Processes Underlying Avian Influenza Viruses in Chicken and Duck.Biology · 2022Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
TGF-β signaling is essential in many processes, including immune surveillance, and its dysregulation controls various diseases, including cancer, fibrosis, and inflammation. Studying the innate host defense, which functions in most cell types, we found that RLR signaling represses TGF-β responses. This regulation is mediated by activated IRF3, using a dual mechanism of IRF3-directed suppression. Activated IRF3 interacts with Smad3, thus inhibiting TGF-β-induced Smad3 activation and, in the nucleus, disrupts functional Smad3 transcription complexes by competing with coregulators. Consequently, IRF3 activation by innate antiviral signaling represses TGF-β-induced growth inhibition, gene regulation and epithelial-mesenchymal transition, and the generation of Treg effector lymphocytes from naive CD4(+) lymphocytes. Conversely, silencing IRF3 expression enhances epithelial-mesenchymal transition, TGF-β-induced Treg cell differentiation upon virus infection, and Treg cell generation in vivo. We present a mechanism of regulation of TGF-β signaling by the antiviral defense, with evidence for its role in immune tolerance and cancer cell behavior.
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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.