Tumor necrosis factor (TNF) is one of the few cytokines successfully targeted by therapies against inflammatory diseases. However, blocking this well studied and pleiotropic ligand can cause dramatic side-effects. Here, we reason that a systems-level proteomic analysis of TNF signaling could dissect its diverse functions and offer a base for developing more targeted therapies. Therefore, we combine phosphoproteomics time course experiments with subcellular localization and kinase inhibitor analysis to identify functional modules of protein phosphorylation. The majority of regulated phosphorylation events can be assigned to an upstream kinase by inhibiting master kinases. Spatial proteomics reveals phosphorylation-dependent translocations of hundreds of proteins upon TNF stimulation. Phosphoproteome analysis of TNF-induced apoptosis and necroptosis uncovers a key role for transcriptional cyclin-dependent kinase activity to promote cytokine production and prevent excessive cell death downstream of the TNF signaling receptor. This resource of TNF-induced pathways and sites can be explored at http://tnfviewer.biochem.mpg.de/ .
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523534 | PMC |
| http://dx.doi.org/10.1038/s41467-021-26289-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
SERT-Deficient Mice Fed Western Diet Reveal Altered Metabolic and Pro-Inflammatory Responses of the Liver: A Link to Abnormal Behaviors.
Front Biosci (Landmark Ed)
January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
View Article and Find Full Text PDFHIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature.
Front Biosci (Landmark Ed)
January 2025
Department of Pathology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larissa, Greece.
Background: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy.
Methods: We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis.
Remimazolam Combined with Andrographolide Improve Postoperative Cognitive Dysfunction in Rats after Cardiopulmonary Bypass through the AMPK/SIRT1 Signaling Pathway.
J Integr Neurosci
January 2025
Department of Anesthesia, Hangzhou Plastic Surgery Hospital, 310000 Hangzhou, Zhejiang, China.
Introduction: The effects of remimazolam (Re) in combination with andrographolide (AP) on learning, memory, and motor abilities in rats following cardiopulmonary bypass (CPB) surgery were studied.
Methods: We hypothesized that the combination of Re and AP could improve postoperative cognitive dysfunction (POCD) in rats after CPB by modulating nervous system inflammation. Cognitive function was assessed using the Morris Water Maze test, and the concentrations of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA).
Molecular Mechanisms and Therapeutic Potential of Mulberry Fruit Extract in High-Fat Diet-Induced Male Reproductive Dysfunction: A Comprehensive Review.
Nutrients
January 2025
Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
High-fat diet (HFD)-induced obesity represents a significant challenge to male reproductive health, affecting approximately 13% of the global adult population. This comprehensive review synthesizes current evidence regarding mulberry ( L.) fruit extract's therapeutic potential for HFD-induced male reproductive dysfunction.
View Article and Find Full Text PDFMolecular Mechanisms Underlying Neuroinflammation Intervention with Medicinal Plants: A Critical and Narrative Review of the Current Literature.
Pharmaceuticals (Basel)
January 2025
Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Marília (UNIMAR), Marília 17525-902, São Paulo, Brazil.
Neuroinflammation is a key factor in the progression of neurodegenerative diseases, driven by the dysregulation of molecular pathways and activation of the brain's immune system, resulting in the release of pro-inflammatory and oxidative molecules. This chronic inflammation is exacerbated by peripheral leukocyte infiltration into the central nervous system. Medicinal plants, with their historical use in traditional medicine, have emerged as promising candidates to mitigate neuroinflammation and offer a sustainable alternative for addressing neurodegenerative conditions in a green healthcare framework.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!