ArticleScience signaling2016
TNF-insulin crosstalk at the transcription factor GATA6 is revealed by a model that links signaling and transcriptomic data tensors.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
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- AI-powered simulation-based inference of a genuinely spatial-stochastic gene regulation model of early mouse embryogenesis.PLoS computational biology · 2024Article
- The structure is the message: Preserving experimental context through tensor decomposition.Cell systems · 2024Review
- Tensor modeling of MRSA bacteremia cytokine and transcriptional patterns reveals coordinated, outcome-associated immunological programs.PNAS nexus · 2024Article
- Article
- Biphasic JNK-Erk signaling separates the induction and maintenance of cell senescence after DNA damage induced by topoisomerase II inhibition.Cell systems · 2023Article
- Tensor-based insights into systems immunity and infectious disease.Trends in immunology · 2023Article
- Tensor-structured decomposition improves systems serology analysis.Molecular systems biology · 2021Article
- Progress in mimicking brain microenvironments to understand and treat neurological disorders.APL bioengineering · 2021Article
- Direct conversion of porcine primary fibroblasts into hepatocyte-like cells.Scientific reports · 2021Article
- Data-Driven Computational Modeling Identifies Determinants of Glioblastoma Response to SHP2 Inhibition.Cancer research · 2021Article
- Contribution of GATA6 to homeostasis of the human upper pilosebaceous unit and acne pathogenesis.Nature communications · 2020Article
- Sporadic activation of an oxidative stress-dependent NRF2-p53 signaling network in breast epithelial spheroids and premalignancies.Science signaling · 2020Article
- A Novel STAT3-Mediated GATA6 Pathway Contributes toOxidative medicine and cellular longevity · 2020Article
- Robust latent-variable interpretation of in vivo regression models by nested resampling.Scientific reports · 2019Article
- FOXO1 degradation via G9a-mediated methylation promotes cell proliferation in colon cancer.Nucleic acids research · 2019Article
- The extracellular matrix as a key regulator of intracellular signalling networks.British journal of pharmacology · 2019Review
- A computational analysis of dynamic, multi-organ inflammatory crosstalk induced by endotoxin in mice.PLoS computational biology · 2018Article
- Roles of glycosaminoglycans as regulators of ligand/receptor complexes.Open biology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Signal transduction networks coordinate transcriptional programs activated by diverse extracellular stimuli, such as growth factors and cytokines. Cells receive multiple stimuli simultaneously, and mapping how activation of the integrated signaling network affects gene expression is a challenge. We stimulated colon adenocarcinoma cells with various combinations of the cytokine tumor necrosis factor (TNF) and the growth factors insulin and epidermal growth factor (EGF) to investigate signal integration and transcriptional crosstalk. We quantitatively linked the proteomic and transcriptomic data sets by implementing a structured computational approach called tensor partial least squares regression. This statistical model accurately predicted transcriptional signatures from signaling arising from single and combined stimuli and also predicted time-dependent contributions of signaling events. Specifically, the model predicted that an early-phase, AKT-associated signal downstream of insulin repressed a set of transcripts induced by TNF. Through bioinformatics and cell-based experiments, we identified the AKT-repressed signal as glycogen synthase kinase 3 (GSK3)-catalyzed phosphorylation of Ser(37) on the long form of the transcription factor GATA6. Phosphorylation of GATA6 on Ser(37) promoted its degradation, thereby preventing GATA6 from repressing transcripts that are induced by TNF and attenuated by insulin. Our analysis showed that predictive tensor modeling of proteomic and transcriptomic data sets can uncover pathway crosstalk that produces specific patterns of gene expression in cells receiving multiple stimuli.
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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 Socratic graph.