ArticleClinical and translational medicine2021
SMYD2-mediated TRAF2 methylation promotes the NF-κB signaling pathways in inflammatory diseases.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 31 citations in OpenAlex.
- Olive (Olea europaea) phenolics for the control of psoriasis via targeting SMYD2 and IL-17A protein-protein interaction networks.Journal of natural medicines · 2026Article
- Article
- TIFA: a signaling hub linking inflammation, innate immunity, and human disease.Frontiers in immunology · 2026Review
- A Novel Inhibitor of Methyltransferase SMYD2, AZ505 Protects Against Peritoneal Fibrosis in Mice.Clinical and experimental pharmacology & physiology · 2025Article
- SMYD2 Promotes Renal Tubular Cell Apoptosis and Chronic Kidney Disease Following Cisplatin Nephrotoxicity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Histone methyltransferase SMYD2 regulates the activation of hepatic stellate cells by activating TLR4 signaling.Scientific reports · 2025Article
- The Role of Post-Translational Modifications in Necroptosis.Biomolecules · 2025Review
- GRK2 activates TRAF2-NF-Acta pharmaceutica Sinica. B · 2025Article
- Novel regulation mechanism of histone methyltransferase SMYD5 in rheumatoid arthritis.Cellular & molecular biology letters · 2025Article
- Impact of exercise-induced DNA damage repair on age-related muscle weakness and sarcopenia.Frontiers in genetics · 2025Review
- RIPK1 in necroptosis and recent progress in related pharmaceutics.Frontiers in immunology · 2025Review
- SMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance.Experimental & molecular medicine · 2024Review
- Hydrogen Sulfide can Scavenge Free Radicals to Improve Spinal Cord Injury by Inhibiting the p38MAPK/mTOR/NF-κB Signaling Pathway.Neuromolecular medicine · 2024Review
- ASH2L upregulation contributes to diabetic endothelial dysfunction in mice through STEAP4-mediated copper uptake.Acta pharmacologica Sinica · 2024Article
- Lysine methyltransferase SMYD2 enhances androgen receptor signaling to modulate CRPC cell resistance to enzalutamide.Oncogene · 2024Article
- Identification of diagnostic genes and drug prediction in metabolic syndrome-associated rheumatoid arthritis by integrated bioinformatics analysis, machine learning, and molecular docking.Frontiers in immunology · 2024Article
- Signaling pathways in rheumatoid arthritis: implications for targeted therapy.Signal transduction and targeted therapy · 2023Review
- TRAF2 as a key candidate gene in clinical hepatitis B-associated liver fibrosis.Frontiers in molecular biosciences · 2023Article
- Cardiovascular hemodynamics in mice with tumor necrosis factor receptor-associated factor 2 mediated cytoprotection in the heart.Frontiers in cardiovascular medicine · 2023Article
- Histone methyltransferase Smyd2 drives vascular aging by its enhancer-dependent activity.Aging · 2022Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
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Abstract
backgroundThe methylation of lysine residues has been involved in the multiple biological and diseases processes. Recently, some particular non-histone proteins have been elucidated to be methylated by SMYD2, a SET and MYND domain protein with lysine methyltransferase activity.
methodsSMYD2 was evaluated in synovial tissue and cells derived from rheumatoid arthritis patients. We confirmed TRAF2 could be methylated by SMYD2 using Mass spectrometry, pull-down, immunoprecipitation, methyltransferase assay, ubiquitination assay, luciferase reporter assays, and western blot analyses. Using loss- and gain-of function studies, we explored the biological functions of SMYD2 in vitro and in vivo. Using acute and chronic inflammation with different mice models to determine the impact of SMYD2.
resultsHere, we first time confirmed that the cytoplasmic protein TRAF2 as the kernel node for NF-κB signaling pathway could be methylated by SMYD2. SMYD2-mediated TRAF2 methylation contributed to the durative sensitization of NF-κB signaling transduction through restraining its own proteolysis and enhancing the activity. In addition, we found knocking down of SMYD2 has different degrees of mitigation in acute and chronic inflammation mice models. Furthermore, as the lysine-specific demethylase, LSD1 could resist methylation on TRAF2 induced by SMYD2.
conclusionsOur data uncovered an unprecedented cytoplasmic protein network that employed methylation of TRAF2 for the maintenance of NF-κB activation during inflammatory diseases.
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