ArticleScience signaling2018
Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Zero-shot de novo peptide sequencing with open posttranslational modification discovery.Nature biotechnology · 2026Article
- Machine learning-driven prediction of substrates for enzymes introducing or removing protein post-translational modifications.Communications chemistry · 2025Article
- The proteomic landscape of diffuse midline glioma highlights the therapeutic potential of non-histone protein methyltransferases.Neuro-oncology · 2025Article
- Quantitative Analysis of Nonhistone Lysine Methylation Sites and Lysine Demethylases in Breast Cancer Cell Lines.Journal of proteome research · 2025Article
- Posttranslational Modifications ofPharmacological reviews · 2024Review
- Quantitative analysis of non-histone lysine methylation sites and lysine demethylases in breast cancer cell lines.bioRxiv : the preprint server for biology · 2024Article
- Craniofacial chondrogenesis in organoids from human stem cell-derived neural crest cells.iScience · 2024Article
- Extracellular Vesicle Protein Expression in Doped Bioactive Glasses: Further Insights Applying Anomaly Detection.International journal of molecular sciences · 2024Article
- IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation.Oncology research · 2024Article
- Proteomics Applications inPathogens (Basel, Switzerland) · 2023Review
- Network models of protein phosphorylation, acetylation, and ubiquitination connect metabolic and cell signaling pathways in lung cancer.PLoS computational biology · 2023Article
- Lactoferrin suppresses the progression of colon cancer under hyperglycemia by targeting WTAP/mJournal of translational medicine · 2023Article
- Control of protein stability by post-translational modifications.Nature communications · 2023Review
- qPTM: an updated database for PTM dynamics in human, mouse, rat and yeast.Nucleic acids research · 2023Article
- Fourier-transform ion cyclotron resonance mass spectrometry for characterizing proteoforms.Mass spectrometry reviews · 2022Review
- Optimal regulation of tumour-associated neutrophils in cancer progression.Royal Society open science · 2022Article
- Hsp90 interaction networks in fungi-tools and techniques.FEMS yeast research · 2021Review
- The Human Melanoma Proteome Atlas-Complementing the melanoma transcriptome.Clinical and translational medicine · 2021Article
- Co-occurrence of Protein Crotonylation and 2-Hydroxyisobutyrylation in the Proteome of End-Stage Renal Disease.ACS omega · 2021Article
- Counterion Optimization Dramatically Improves Selectivity for Phosphopeptides and Glycopeptides in Electrostatic Repulsion-Hydrophilic Interaction Chromatography.Analytical chemistry · 2021Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs. We used the t-distributed stochastic neighbor embedding (t-SNE) method to identify PTM clusters and then integrated each with known protein-protein interactions (PPIs) to elucidate functional cell signaling pathways. The CFN identified known and previously unknown cell signaling pathways in lung cancer cells that were not present in normal lung epithelial tissue. In various proteins modified by more than one type of PTM, the incidence of those PTMs exhibited inverse relationships, suggesting that molecular exclusive "OR" gates determine a large number of signal transduction events. We also showed that the acetyltransferase EP300 appears to be a hub in the network of pathways involving different PTMs. In addition, the data shed light on the mechanism of action of geldanamycin, an HSP90 inhibitor. Together, the findings reveal that cell signaling pathways mediated by acetylation, methylation, and phosphorylation regulate the cytoskeleton, membrane traffic, and RNA binding protein-mediated control of gene expression.
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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.