ArticleMolecular systems biology2020
An incoherent feedforward loop interprets NFκB/RelA dynamics to determine TNF-induced necroptosis decisions.
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 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- RIPK3 Orchestrates Scar-Associated Macrophage Dysfunction to Drive Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Trainable computation in molecular networks.bioRxiv : the preprint server for biology · 2025Article
- Review
- Targeting the Met-RIPK1 signaling axis to enforce apoptosis and necroptosis in colorectal cancer.Cell death & disease · 2025Article
- Transcriptional remodeling shapes therapeutic vulnerability to necroptosis in acute lymphoblastic leukemia.Blood · 2025Article
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- An Anti-CD147 Antibody-Drug Conjugate Mehozumab-DM1 is Efficacious Against Hepatocellular Carcinoma in Cynomolgus Monkey.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- C-Terminal Hsp90 Inhibitors Overcome MEK and BRAF Inhibitor Resistance in Melanoma.Journal of cellular and molecular medicine · 2025Article
- Linking signaling dynamics and cell fate decisions through single-cell imaging: evidence and challenges.Frontiers in cell and developmental biology · 2025Review
- NF-κB: master regulator of cellular responses in health and disease.Immunity & inflammation · 2025Review
- RIPK3 signaling and its role in regulated cell death and diseases.Cell death discovery · 2024Review
- A logic-incorporated gene regulatory network deciphers principles in cell fate decisions.eLife · 2024Article
- Cellular heterogeneity in TNF/TNFR1 signalling: live cell imaging of cell fate decisions in single cells.Cell death & disease · 2024Review
- Article
- Modulating the dynamics of NFκB and PI3K enhances the ensemble-level TNFR1 signaling mediated apoptotic response.NPJ systems biology and applications · 2023Article
- Incoherent merger network for robust ratiometric gene expression response.Nucleic acids research · 2023Article
- Model certainty in cellular network-driven processes with missing data.PLoS computational biology · 2023Article
- A biochemical necroptosis model explains cell-type-specific responses to cell death cues.Biophysical journal · 2023Article
- Network pharmacology-based analysis of the mechanism ofPharmaceutical biology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Balancing cell death is essential to maintain healthy tissue homeostasis and prevent disease. Tumor necrosis factor (TNF) not only activates nuclear factor κB (NFκB), which coordinates the cellular response to inflammation, but may also trigger necroptosis, a pro-inflammatory form of cell death. Whether TNF-induced NFκB affects the fate decision to undergo TNF-induced necroptosis is unclear. Live-cell microscopy and model-aided analysis of death kinetics identified a molecular circuit that interprets TNF-induced NFκB/RelA dynamics to control necroptosis decisions. Inducible expression of TNFAIP3/A20 forms an incoherent feedforward loop to interfere with the RIPK3-containing necrosome complex and protect a fraction of cells from transient, but not long-term TNF exposure. Furthermore, dysregulated NFκB dynamics often associated with disease diminish TNF-induced necroptosis. Our results suggest that TNF's dual roles in either coordinating cellular responses to inflammation, or further amplifying inflammation are determined by a dynamic NFκB-A20-RIPK3 circuit, that could be targeted to treat inflammation and cancer.
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Registered trials
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.