ArticleMolecular and cellular biology2012
Rb/E2F1 regulates the innate immune receptor Toll-like receptor 3 in epithelial cells.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Immune Checkpoint Blockade Outcome in Small-Cell Lung Cancer and Its Relationship With Retinoblastoma Mutation Status and Function.JCO precision oncology · 2022Trial
- The TRIM22-CDT2 axis is the key mediator of the p53-Rb signals in growth control of HPV-positive cervical carcinoma cells.Neoplasia (New York, N.Y.) · 2025Article
- Mechanisms of immunotherapy resistance in small cell lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Viral and cellular oncogenes promote immune evasion.Oncogene · 2022Review
- Article
- TLR3 Serves as a Prognostic Biomarker and Associates with Immune Infiltration in the Renal Clear Cell Carcinoma Microenvironment.Journal of oncology · 2021Article
- Tumor Milieu Controlled by RB Tumor Suppressor.International journal of molecular sciences · 2020Review
- Unveiling Interindividual Variability of Human Fibroblast Innate Immune Response Using Robust Cell-Based Protocols.Frontiers in immunology · 2020Article
- Ephedrine enhances HIV-1 reactivation from latency through elevating tumor necrosis factor receptor II (TNFRII) expression.Heliyon · 2019Article
- Article
- Simultaneous Transcriptional and Epigenomic Profiling from Specific Cell Types within Heterogeneous Tissues In Vivo.Cell reports · 2017Article
- Emerging roles of p53 and other tumour-suppressor genes in immune regulation.Nature reviews. Immunology · 2016Review
- The Importance of Physiologically Relevant Cell Lines for Studying Virus-Host Interactions.Viruses · 2016Review
- Retinoblastoma tumor suppressor functions shared by stem cell and cancer cell strategies.World journal of stem cells · 2016Review
- Cell-Cycle Regulators and Cell Death in Immunity.Cell host & microbe · 2015Review
- COMMD1/Murr1 reinforces HIV-1 latent infection through IκB-α stabilization.Journal of virology · 2015Article
- The RB tumor suppressor at the intersection of proliferation and immunity: relevance to disease immune evasion and immunotherapy.Cell cycle (Georgetown, Tex.) · 2015Review
- Retinoblastoma protein potentiates the innate immune response in hepatocytes: significance for hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2014Article
- Macrophages, inflammation, and tumor suppressors: ARF, a new player in the game.Mediators of inflammation · 2012Review
- Development of Therapeutic-Grade Small Interfering RNAs by Chemical Engineering.Frontiers in genetics · 2012Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor suppressor genes regulate the antiviral host defense through molecular mechanisms that are not yet well explored. Here, we show that the tumor suppressor retinoblastoma (Rb) protein positively regulates Toll-like receptor 3 (TLR3) expression, the sensing receptor for viral double-stranded RNA and poly(I · C). TLR3 expression was lower in Rb knockout (Rb(-/-)) mouse embryonic fibroblasts (MEF) and in mammalian epithelial cells transfected with Rb small-interfering RNA (siRNA) than in control cells. Consequently, induction of cytokines interleukin-8 and beta interferon after poly(I · C) stimulation was impaired in Rb(-/-) MEF and Rb siRNA-transfected cells compared to controls. TLR3 promoter analysis showed that Rb modulates the transcription factor E2F1, which directly binds to the proximal promoter of TLR3. Exogenous addition of E2F1 decreased TLR3 promoter activity, while Rb dose dependently curbed the effect of E2F1. Interestingly, poly(I · C) increased the Rb expression, and the poly(I · C)-induced TLR3 expression was impaired in Rb-depleted cells, suggesting the importance of Rb in TLR3 induction by poly(I · C). Together, these data indicated that E2F1 suppresses TLR3 transcription, but during immune stimulation, Rb is upregulated to block the inhibitory effect of E2F1 on TLR3, highlighting a role of Rb-E2F1 axis in the innate immune response in epithelial cells.
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Registered trials
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