ArticleProceedings of the National Academy of Sciences of the United States of America2021
Regulation of TLR4 signaling through the TRAF6/sNASP axis by reversible phosphorylation mediated by CK2 and PP4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- PP4 deficiency drives airway epithelial senescence via the PERK-eIF2α-ATF4-p21 axis in severe asthma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- PP4 modulates macrophage-neutrophil crosstalk to restrict CCL5 -driven NETosis in sepsis.Redox biology · 2026Article
- CYLD links the TRAF6/sNASP axis to TLR4 signaling in sepsis-induced acute lung injury.Cellular and molecular life sciences : CMLS · 2025Article
- Polyamines protect porcine sperm from lipopolysaccharide-induced mitochondrial dysfunction and apoptosis via casein kinase 2 activation.Journal of animal science · 2025Article
- Protective effect of CK2 against endoplasmic reticulum stress in pancreatic β cells.Diabetology international · 2025Article
- Dendritic Morphology of Developing Hippocampal Neurons in Cyp11a1 Null Mice.Developmental neuroscience · 2025Article
- SCGB1A1 as a novel biomarker and promising therapeutic target for the management of HNSCC.Oncology letters · 2024Article
- The Uridylyl Transferase TUT7-Mediated Accumulation of Exosomal miR-1246 Reprograms TAMs to Support CRC Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Genetic correlations and causal relationships between cardio-metabolic traits and sepsis.Scientific reports · 2024Article
- Review
- Home Dust Mites Promote MUC5AC Hyper-Expression by Modulating the sNASP/TRAF6 Axis in the Airway Epithelium.International journal of molecular sciences · 2022Article
- PEP-sNASP Peptide Alleviates LPS-Induced Acute Lung Injury Through the TLR4/TRAF6 Axis.Frontiers in medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recognition of invading pathogens by Toll-like receptors (TLRs) activates innate immunity through signaling pathways that involved multiple protein kinases and phosphatases. We previously demonstrated that somatic nuclear autoantigenic sperm protein (sNASP) binds to TNF receptor-associated factor 6 (TRAF6) in the resting state. Upon TLR4 activation, a signaling complex consisting of TRAF6, sNASP, interleukin (IL)-1 receptor-associated kinase 4, and casein kinase 2 (CK2) is formed. CK2 then phosphorylates sNASP to release phospho-sNASP (p-sNASP) from TRAF6, initiating downstream signaling pathways. Here, we showed that protein phosphatase 4 (PP4) is the specific sNASP phosphatase that negatively regulates TLR4-induced TRAF6 activation and its downstream signaling pathway. Mechanistically, PP4 is directly recruited by phosphorylated sNASP to dephosphorylate p-sNASP to terminate TRAF6 activation. Ectopic expression of PP4 specifically inhibited sNASP-dependent proinflammatory cytokine production and downstream signaling following bacterial lipopolysaccharide (LPS) treatment, whereas silencing PP4 had the opposite effect. Primary macrophages and mice infected with recombinant adenovirus carrying a gene encoding PP4 (Ad-PP4) showed significant reduction in IL-6 and TNF-α production. Survival of Ad-PP4-infected mice was markedly increased due to a better ability to clear bacteria in a sepsis model. These results indicate that the serine/threonine phosphatase PP4 functions as a negative regulator of innate immunity by regulating the binding of sNASP to TRAF6.
Indexed as
Identifiers
What OpenQuestion holds
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.