ArticleThe Journal of experimental medicine2017
p38 inhibition provides anti-DNA virus immunity by regulation of USP21 phosphorylation and STING activation.
Article in The Journal of experimental medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 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
76 citing papers in PubMed, 99 citations in OpenAlex.
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- TANK potentiates antiviral innate immunity by recruiting deubiquitinase USP46 to activate IKKε.PLoS pathogens · 2026Article
- USP21 functions as an oncogenic regulator of the Mdm2-p53 axis in colorectal cancer.Cell death discovery · 2026Article
- USP39 promotes antiviral defense through post-transcriptional control of RIG-I and stabilization of STING.PLoS biology · 2026Article
- The cGAS-STING pathway in pulmonary infectious and sterile inflammation: differences, connections, and therapeutic implications.Frontiers in immunology · 2026Review
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- The Ubiquitin Script: writing protein fates in chains.Essays in biochemistry · 2025Review
- Mechanism of USP21 autoinhibition and histone H2AK119 deubiquitination.Science advances · 2025Article
- The role of absent in melanoma 2 (AIM2) in cardiovascular diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2025Review
- HPV16 E7 inhibits HBD2 expression by down-regulation of ASK1-p38 MAPK pathway in cervical cancer.Virology journal · 2025Article
- Deubiquitination enzyme USP35 negatively regulates MAVS signaling to inhibit anti-tumor immunity.Cell death & disease · 2025Article
- Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type-I IFN Signaling.Cancer research · 2025Article
- The role of cGAS-STING pathway ubiquitination in innate immunity and multiple diseases.Frontiers in immunology · 2025Review
- Roles of deubiquitinases in urologic cancers (Review).Oncology letters · 2024Review
- The role of the cGAS-STING signaling pathway in viral infections, inflammatory and autoimmune diseases.Acta pharmacologica Sinica · 2024Review
- Comprehensive analysis of the relationship between ubiquitin-specific protease 21 (USP21) and prognosis, tumor microenvironment infiltration, and therapy response in colorectal cancer.Cancer immunology, immunotherapy : CII · 2024Article
- Pulsed Electric Fields Induce STING Palmitoylation and Polymerization Independently of Plasmid DNA Electrotransfer.Pharmaceutics · 2024Article
- cGLRs Join Their Cousins of Pattern Recognition Receptor Family to Regulate Immune Homeostasis.International journal of molecular sciences · 2024Review
- Emerging mechanisms and implications of cGAS-STING signaling in cancer immunotherapy strategies.Cancer biology & medicine · 2024Review
16 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
19 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulator of IFN genes (STING) is a central adaptor protein that mediates the innate immune responses to DNA virus infection. Although ubiquitination is essential for STING function, how the ubiquitination/deubiquitination system is regulated by virus infection to control STING activity remains unknown. In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus-induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. Inhibition of p38 MAPK enhanced the production of IFNs in response to virus infection and protected mice from lethal HSV-1 infection. Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses.
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.