ArticleThe Journal of experimental medicine2008
Acetylation of mitogen-activated protein kinase phosphatase-1 inhibits Toll-like receptor signaling.
Article in The Journal of experimental medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 186 citations in OpenAlex.
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- GR/P300 Regulates MKP1 Signaling Pathway and Mediates Depression-like Behavior in Prenatally Stressed Offspring.Molecular neurobiology · 2024Article
- MAPK phosphatase 1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution.The Journal of clinical investigation · 2024Article
- The Role of Selected Epigenetic Pathways in Cardiovascular Diseases as a Potential Therapeutic Target.International journal of molecular sciences · 2023Review
- Article
- Research Progress on the Positive and Negative Regulatory Effects of Rhein on the Kidney: A Review of Its Molecular Targets.Molecules (Basel, Switzerland) · 2022Review
- Cardiovascular protection by SGLT2 inhibitors - Do anti-inflammatory mechanisms play a role?Molecular metabolism · 2022Review
- Histone modifiers at the crossroads of oncolytic and oncogenic viruses.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Review
- Maximizing Depth of PTM Coverage: Generating Robust MS Datasets for Computational Prediction Modeling.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Reciprocal regulation of endothelial-mesenchymal transition by MAPK7 and EZH2 in intimal hyperplasia and coronary artery disease.Scientific reports · 2021Article
- Fluoxetine regulates eEF2 activity (phosphorylation) via HDAC1 inhibitory mechanism in an LPS-induced mouse model of depression.Journal of neuroinflammation · 2021Article
- Comparative Analysis of Global Proteome and Lysine Acetylome Between Naive CD4Frontiers in immunology · 2021Article
- A dissection of SARS‑CoV2 with clinical implications (Review).International journal of molecular medicine · 2020Review
- AGK2 Alleviates Lipopolysaccharide Induced Neuroinflammation through Regulation of Mitogen-Activated Protein Kinase Phosphatase-1.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Article
- ERK Dephosphorylation through MKP1 Deacetylation by SIRT1 Attenuates RAS-Driven Tumorigenesis.Cancers · 2020Article
- HDAC3 Regulates Gingival Fibroblast Inflammatory Responses in Periodontitis.Journal of dental research · 2020Article
- Global Lysine Crotonylation Alterations of Host Cell Proteins Caused byFrontiers in cellular and infection microbiology · 2020Article
- Dual-Specificity Phosphatase Regulation in Neurons and Glial Cells.International journal of molecular sciences · 2019Review
- Functions and mechanisms of non-histone protein acetylation.Nature reviews. Molecular cell biology · 2019Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The mitogen-activated protein kinase (MAPK) pathway plays a critical role in Toll-like receptor (TLR) signaling. MAPK phosphatase-1 (MKP-1) inhibits the MAPK pathway and decreases TLR signaling, but the regulation of MKP-1 is not completely understood. We now show that MKP-1 is acetylated, and that acetylation regulates its ability to interact with its substrates and deactivate inflammatory signaling. We found that LPS activates acetylation of MKP-1. MKP-1 is acetylated by p300 on lysine residue K57 within its substrate-binding domain. Acetylation of MKP-1 enhances its interaction with p38, thereby increasing its phosphatase activity and interrupting MAPK signaling. Inhibition of deacetylases increases MKP-1 acetylation and blocks MAPK signaling in wild-type (WT) cells; however, deacetylase inhibitors have no effect in cells lacking MKP-1. Furthermore, histone deacetylase inhibitors reduce inflammation and mortality in WT mice treated with LPS, but fail to protect MKP-1 knockout mice. Our data suggest that acetylation of MKP-1 inhibits innate immune signaling. This pathway may be an important therapeutic target in the treatment of inflammatory diseases.
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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.