ArticleCell reports2013
Protein phosphatase 2A catalytic subunit α plays a MyD88-dependent, central role in the gene-specific regulation of endotoxin tolerance.
Article in Cell reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Pde1b controls cyclic nucleotide signaling in cDC1 and macrophages to regulate immune responses.EMBO reports · 2026Article
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- Divergent Processing of Cell Stress Signals as the Basis of Cancer Progression: Licensing NFκB on Chromatin.International journal of molecular sciences · 2024Review
- Article
- The oncogenic human B-cell lymphoma MYD88 L265P mutation genocopies activation by phosphorylation at the Toll/interleukin-1 receptor (TIR) domain.Blood cancer journal · 2023Article
- Inhibition of Sphingosine Kinase 2 Results in PARK2-Mediated Mitophagy and Induces Apoptosis in Multiple Myeloma.Current oncology (Toronto, Ont.) · 2023Article
- Heterologous Expression and Assembly of Human TLR Signaling Components inBiomolecules · 2021Article
- MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography.Nature communications · 2021Article
- Protein phosphatases in TLR signaling.Cell communication and signaling : CCS · 2021Review
- HOxidative medicine and cellular longevity · 2021Review
- Article
- PP2Ac Modulates AMPK-Mediated Induction of Autophagy inInternational journal of molecular sciences · 2019Article
- An ANGPTL4-ceramide-protein kinase Cζ axis mediates chronic glucocorticoid exposure-induced hepatic steatosis and hypertriglyceridemia in mice.The Journal of biological chemistry · 2019Article
- The glucocorticoid-Angptl4-ceramide axis induces insulin resistance through PP2A and PKCζ.Science signaling · 2017Article
- Myeloid-Specific Gene Deletion of Protein Phosphatase 2A Magnifies MyD88- and TRIF-Dependent Inflammation following Endotoxin Challenge.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Epigenetic Mechanisms Governing Innate Inflammatory Responses.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2016Review
- Phosphatase PP2A is requisite for the function of regulatory T cells.Nature immunology · 2016Article
- Proteomic dissection of LPS-inducible, PHF8-dependent secretome reveals novel roles of PHF8 in TLR4-induced acute inflammation and T cell proliferation.Scientific reports · 2016Article
- DCAF1 controls T-cell function via p53-dependent and -independent mechanisms.Nature communications · 2016Article
- Endotoxin Tolerance Inhibits Lyn and c-Src Phosphorylation and Association with Toll-Like Receptor 4 but Increases Expression and Activity of Protein Phosphatases.Journal of innate immunity · 2016Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
MyD88, the intracellular adaptor of most TLRs, mediates either proinflammatory or immunosuppressive signaling that contributes to chronic inflammation-associated diseases. Although gene-specific chromatin modifications regulate inflammation, the role of MyD88 signaling in establishing such epigenetic landscapes under different inflammatory states remains elusive. Using quantitative proteomics to enumerate the inflammation-phenotypic constituents of the MyD88 interactome, we found that in endotoxin-tolerant macrophages, protein phosphatase 2A catalytic subunit α (PP2Ac) enhances its association with MyD88 and is constitutively activated. Knockdown of PP2Ac prevents suppression of proinflammatory genes and resistance to apoptosis. Through site-specific dephosphorylation, constitutively active PP2Ac disrupts the signal-promoting TLR4-MyD88 complex and broadly suppresses the activities of multiple proinflammatory/proapoptotic pathways as well, shifting proinflammatory MyD88 signaling to a prosurvival mode. Constitutively active PP2Ac translocated with MyD88 into the nuclei of tolerant macrophages establishes the immunosuppressive pattern of chromatin modifications and represses chromatin remodeling to selectively silence proinflammatory genes, coordinating the MyD88-dependent inflammation control at both signaling and epigenetic levels under endotoxin-tolerant conditions.
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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.