ArticleThe Journal of biological chemistry2013
The catalytic subunit of protein phosphatase 2A (PP2Ac) promotes DNA hypomethylation by suppressing the phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/phosphorylated ERK/DNMT1 protein pathway in T-cells from controls and systemic lupus erythematosus patients.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 105 citations in OpenAlex.
- Efficacy of mebendazole in the spontaneous NZBxNZWF1 animal model of systemic lupus erythematosus.Scientific reports · 2026Article
- The microbiota-systemic lupus erythematosus axis: mechanisms, diagnostics, and therapeutic frontiers.Frontiers in immunology · 2026Review
- The role of epigenetic regulation in cuproptosis, ferroptosis and NETosis in the pathogenesis of autoimmune diseases.Apoptosis : an international journal on programmed cell death · 2025Review
- Deregulated nutrient response in ttntv cardiomyopathy can be repaired via Erk inhibition for cardioprotective effects.Journal of molecular and cellular cardiology · 2025Article
- Langerhans cells infiltration in lymph nodes of patients with systemic lupus erythematosus.Lupus science & medicine · 2025Article
- Gluconolactone restores immune regulation and alleviates skin inflammation in lupus-prone mice and in patients with cutaneous lupus.Science translational medicine · 2025Article
- The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- Role of DNA Methylation in the Pathogenesis of Skin Disorders: Mechanisms, Inhibitors of Methylation-Related Enzyme, and Molecular Docking Studies.BioMed research international · 2025Review
- American College of Rheumatology White Paper: The Effects of Climate Change on Rheumatic Conditions-An Evolving Landscape and a Path Forward.Arthritis & rheumatology (Hoboken, N.J.) · 2024Review
- Epigenetic Dysregulation in the Pathogenesis of Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4International journal of molecular sciences · 2023Review
- Protein phosphatase 2A propels follicular T helper cell development in lupus.Journal of autoimmunity · 2023Article
- PGC7 Regulates Genome-Wide DNA Methylation by Regulating ERK-Mediated Subcellular Localization of DNMT1.International journal of molecular sciences · 2023Article
- Aggression Results in the Phosphorylation of ERK1/2 in the Nucleus Accumbens and the Dephosphorylation of mTOR in the Medial Prefrontal Cortex in Female Syrian Hamsters.International journal of molecular sciences · 2023Article
- Protein Phosphatase 2A: Role in T Cells and Diseases.Journal of immunology research · 2023Review
- Downregulation of CAMK2N1 due to DNA Hypermethylation Mediated by DNMT1 that Promotes the Progression of Prostate Cancer.Journal of oncology · 2023Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- SARS-CoV-2 Interaction with Human DNA Methyl Transferase 1: A Potential Risk for Increasing the Incidence of Later Chronic Diseases in the Survived Patients.International journal of preventive medicine · 2022Article
- Maternal methionine supplementation during gestation alters alternative splicing and DNA methylation in bovine skeletal muscle.BMC genomics · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
DNA hypomethylation is a characteristic feature of systemic lupus erythematosus (SLE) immune cells. Numerous reports have implicated the involvement of the MEK/ERK pathway in the reduction of DNA methyltransferase (DNMT) expression, hence inducing the transcription of methylation-sensitive genes in SLE patients. However, the molecular mechanisms involved remain unclear. Here, we investigated whether the catalytic subunit of protein phosphatase 2A (PP2Ac), which is overexpressed in SLE T-cells, contributes to reduced DNA methylation. We show that both chemical suppression and siRNA silencing of PP2Ac in T-cells resulted in sustained phosphorylation of MEK and ERK following stimulation with phorbol 12-myristate 13-acetate and ionomycin. Furthermore, PP2Ac suppression resulted in increased DNMT enzyme activity, DNA hypermethylation, and decreased expression of methylation-sensitive genes. Similarly, in SLE T-cells, suppression of PP2Ac resulted in increased MEK/ERK phosphorylation, enhanced DNMT1 expression and suppressed expression of the methylation-sensitive CD70 gene. Our results demonstrate that PP2A regulates DNA methylation by influencing the phosphorylation of MEK/ERK. We propose that enhanced PP2Ac in SLE T-cells may dephosphorylate and activate the signaling pathway upstream of DNMT1, thus disturbing the tight control of methylation-sensitive genes, which are involved in SLE pathogenesis.
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