ArticleAutophagy2023
Tegument protein UL21 of alpha-herpesvirus inhibits the innate immunity by triggering CGAS degradation through TOLLIP-mediated selective autophagy.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 83 citations in OpenAlex.
- Transglutaminase 2 regulates innate immunity: mechanisms and therapeutic implications.Oncoimmunology · 2026Review
- Herpesviruses and autophagy: An intracellular conflict.Virulence · 2026Review
- The cGAS-STING/MITA pathway in innate antiviral immunity and beyond.Cell insight · 2026Review
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- The role of E3 ubiquitin ligases in selective types of macroautophagy.EMBO reports · 2026Review
- Cell death network regulation in HSV infection: immune evasion versus host defense.Apoptosis : an international journal on programmed cell death · 2026Review
- TOLLIP Inhibits Psoriasis Progression via Suppressing PKM2-Mediated Glycolysis in Keratinocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Alpha-herpesvirus UL55 synergizes with ICP27 to suppress type I interferon production through conserved and host-adapted mechanisms.Journal of virology · 2026Article
- Coronavirus M Protein Hijacks Toll-Interacting Protein (TOLLIP) to Suppress NF-κB Signaling and Promote Immune Evasion.MedComm · 2026Article
- Mitochondria-associated endoplasmic reticulum membrane (MAM): roles in innate immunity dysregulation.Cell communication and signaling : CCS · 2026Review
- Coronavirus infectious bronchitis virus spike protein inhibits FUNDC1-mediated mitophagy to prevent nucleocapsid protein degradation.Journal of virology · 2026Article
- Targeting IRF1-TRIM21 axis enhances anti-tumor immunity by promoting ubiquitin-mediated degradation of FGL1 in non-small cell lung cancer.Communications biology · 2026Article
- Construction of a Three-Dimensional Culture Model of HSV-1 Based on the Nano-Self-Assembling Peptide RADA16-I and Preliminary Exploration of the Relationship Between HSV-1 and Autophagy.Microorganisms · 2026Article
- Proximity labelling identifies proteins associated with HSV-2 pUL21 at early and late times after infection.PLoS pathogens · 2026Article
- Picornavirus VP2 protein suppresses innate immunity through selective autophagic degradation of IKBKE/IKKε.Autophagy · 2026Article
- Divergent Strategies in Innate Immune Evasion: A Comparative Review of Three Alphaherpesvirus Subfamily Members-PRV, HSV-1, and VZV.Transboundary and emerging diseases · 2026Review
- Article
- The PCK2-Traf6-Tollip Axis Restricts PEDV Replication by Orchestrating Selective Autophagic Degradation of the Viral Nucleocapsid Protein.Transboundary and emerging diseases · 2026Article
- Alpha-herpesvirus US1 interacts with cGAS to suppress type I IFN responses and antiviral defense.PLoS pathogens · 2025Article
- Breaking barriers: The cGAS-STING pathway as a novel frontier in cancer immunotherapy.Cancer communications (London, England) · 2025Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha-herpesvirus causes lifelong infections and serious diseases in a wide range of hosts and has developed multiple strategies to counteract the host defense. Here, we demonstrate that the tegument protein UL21 (unique long region 21) in pseudorabies virus (PRV) dampens type I interferon signaling by triggering the degradation of CGAS (cyclic GMP-AMP synthase) through the macroautophagy/autophagy-lysosome pathway. Mechanistically, the UL21 protein scaffolds the E3 ligase UBE3C (ubiquitin protein ligase E3C) to catalyze the K27-linked ubiquitination of CGAS at Lys384, which is recognized by the cargo receptor TOLLIP (toll interacting protein) and degraded in the lysosome. Additionally, we show that the N terminus of UL21 in PRV is dominant in destabilizing CGAS-mediated innate immunity. Moreover, viral tegument protein UL21 in herpes simplex virus type 1 (HSV-1) also displays the conserved inhibitory mechanisms. Furthermore, by using PRV, we demonstrate the roles of UL21 in degrading CGAS to promote viral infection
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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 Socratic graph.