ArticlePLoS computational biology2014
The structural pathway of interleukin 1 (IL-1) initiated signaling reveals mechanisms of oncogenic mutations and SNPs in inflammation and cancer.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
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- Tumor glycosylation engages CD301b-mediated myeloid regulation in breast cancer.Research square · 2026Article
- Immuno-Mechanical Signaling Network Integration in Temporomandibular Joint Pathology: A TMID Conceptual Framework.International journal of molecular sciences · 2026Review
- Image segmentation-based analysis reveals correlation between IL-1RA overexpression and worse survival outcomes in oral squamous cell carcinoma.Scientific reports · 2026Article
- Bone Marrow Mesenchymal Stem Cell Hydrogel-Mediated Fibroblast Reprogramming Restores Intestinal Function in Adhesive Small Bowel Obstruction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Serum Biomarkers in Paediatric Neurosurgery: Traumatic Brain Injury and Beyond.Advances and technical standards in neurosurgery · 2026Article
- CD301b lectin expression in the breast tumor microenvironment augments tumor growth.Research square · 2025Article
- CD301b lectin expression in the breast tumor microenvironment augments tumor growth.bioRxiv : the preprint server for biology · 2025Article
- Hydrocephalus: Molecular and Neuroimaging Biomarkers in Diagnosis and Management.Biomedicines · 2025Review
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Paired blood and brain tissue methylation biomarkers in focal cortical dysplasia.Brain communications · 2025Article
- Identification of PANoptosis-based signature for predicting the prognosis and immunotherapy response in AML.Heliyon · 2024Article
- Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy.Life science alliance · 2024Article
- Triptolide suppresses IL-1β-induced expression of interleukin-8 by inhibiting ROS-Mediated ERK, AP-1, and NF-κB molecules in human gastric cancer AGS cells.Frontiers in oncology · 2024Article
- Role of ErbB and IL-1 signaling pathways in the dermonecrotic lesion induced by Loxosceles sphingomyelinases D.Archives of toxicology · 2023Article
- Structural coverage of the human interactome.Briefings in bioinformatics · 2023Article
- Club cell CREB regulates the goblet cell transcriptional network and pro-mucin effects of IL-1B.Frontiers in physiology · 2023Article
- Inflammatory cytokines as mediators of retinal endothelial barrier dysfunction in non-infectious uveitis.Clinical & translational immunology · 2023Review
- IL-1RAP, a Key Therapeutic Target in Cancer.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
Abstract
Interleukin-1 (IL-1) is a large cytokine family closely related to innate immunity and inflammation. IL-1 proteins are key players in signaling pathways such as apoptosis, TLR, MAPK, NLR and NF-κB. The IL-1 pathway is also associated with cancer, and chronic inflammation increases the risk of tumor development via oncogenic mutations. Here we illustrate that the structures of interfaces between proteins in this pathway bearing the mutations may reveal how. Proteins are frequently regulated via their interactions, which can turn them ON or OFF. We show that oncogenic mutations are significantly at or adjoining interface regions, and can abolish (or enhance) the protein-protein interaction, making the protein constitutively active (or inactive, if it is a repressor). We combine known structures of protein-protein complexes and those that we have predicted for the IL-1 pathway, and integrate them with literature information. In the reconstructed pathway there are 104 interactions between proteins whose three dimensional structures are experimentally identified; only 15 have experimentally-determined structures of the interacting complexes. By predicting the protein-protein complexes throughout the pathway via the PRISM algorithm, the structural coverage increases from 15% to 71%. In silico mutagenesis and comparison of the predicted binding energies reveal the mechanisms of how oncogenic and single nucleotide polymorphism (SNP) mutations can abrogate the interactions or increase the binding affinity of the mutant to the native partner. Computational mapping of mutations on the interface of the predicted complexes may constitute a powerful strategy to explain the mechanisms of activation/inhibition. It can also help explain how an oncogenic mutation or SNP works.
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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.