ArticleMolecular systems biology2020
Disentangling molecular mechanisms regulating sensitization of interferon alpha signal transduction.
Article in Molecular systems biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
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- Pancreatic β-cell FFA2 deficiency suppresses multiple low dose streptozotocin induced diabetes in male mice.Communications biology · 2025Article
- Gene regulatory logic of the interferon-β enhancer is characterized by two selectively deployed modes of transcription factor synergy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Towards an interpretable deep learning model of cancer.NPJ precision oncology · 2025Review
- drexml: A command line tool and Python package for drug repurposing.Computational and structural biotechnology journal · 2024Article
- Basal MET phosphorylation is an indicator of hepatocyte dysregulation in liver disease.Molecular systems biology · 2024Article
- Unraveling IFN-I response dynamics and TNF crosstalk in the pathophysiology of systemic lupus erythematosus.Frontiers in immunology · 2024Article
- High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral response.Life science alliance · 2023Article
- Uncovering specific mechanisms across cell types in dynamical models.PLoS computational biology · 2023Article
- Pharmacological modulators of epithelial immunity uncovered by synthetic genetic tracing of SARS-CoV-2 infection responses.Science advances · 2023Article
- Proofreading does not result in more reliable ligand discrimination in receptor signaling due to its inherent stochasticity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A stimulus-contingent positive feedback loop enables IFN-β dose-dependent activation of pro-inflammatory genes.Molecular systems biology · 2023Article
- Epigenetic signals that direct cell type-specific interferon beta response in mouse cells.Life science alliance · 2023Article
- USP18 is an essential regulator of muscle cell differentiation and maturation.Cell death & disease · 2023Article
- Revising immune cell coordination: Origins and importance of single-cell variation.European journal of immunology · 2022Review
- Stochastic dynamics of Type-I interferon responses.PLoS computational biology · 2022Article
- Deciphering signal transduction networks in the liver by mechanistic mathematical modelling.The Biochemical journal · 2022Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tightly interlinked feedback regulators control the dynamics of intracellular responses elicited by the activation of signal transduction pathways. Interferon alpha (IFNα) orchestrates antiviral responses in hepatocytes, yet mechanisms that define pathway sensitization in response to prestimulation with different IFNα doses remained unresolved. We establish, based on quantitative measurements obtained for the hepatoma cell line Huh7.5, an ordinary differential equation model for IFNα signal transduction that comprises the feedback regulators STAT1, STAT2, IRF9, USP18, SOCS1, SOCS3, and IRF2. The model-based analysis shows that, mediated by the signaling proteins STAT2 and IRF9, prestimulation with a low IFNα dose hypersensitizes the pathway. In contrast, prestimulation with a high dose of IFNα leads to a dose-dependent desensitization, mediated by the negative regulators USP18 and SOCS1 that act at the receptor. The analysis of basal protein abundance in primary human hepatocytes reveals high heterogeneity in patient-specific amounts of STAT1, STAT2, IRF9, and USP18. The mathematical modeling approach shows that the basal amount of USP18 determines patient-specific pathway desensitization, while the abundance of STAT2 predicts the patient-specific IFNα signal response.
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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.