ArticleThe Journal of biological chemistry2020
HDAC6 regulates antibody-dependent intracellular neutralization of viruses via deacetylation of TRIM21.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Regulation of organic anion transporting polypeptide 1B1 transport function by lysine deacetylase 6.Molecular pharmacology · 2026Article
- Histone deacetylase 6 deacetylates and ubiquitinates ATG3 to regulate autophagy.Cell death and differentiation · 2026Article
- Targeting neurodegenerative disease-associated protein aggregation with proximity-inducing modalities.Acta pharmacologica Sinica · 2025Review
- The multilayered control of acetylation during adenovirus-based immunotherapy of cancer.Molecular therapy. Oncology · 2025Review
- DNA-RNA hybrids in inflammation: sources, immune response, and therapeutic implications.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Harnessing Epigenetics: Innovative Approaches in Diagnosing and Combating Viral Acute Respiratory Infections.Pathogens (Basel, Switzerland) · 2025Review
- Beyond Tumors: The Pivotal Role of TRIM Proteins in Chronic Non-Tumor Lung Diseases.Journal of inflammation research · 2025Review
- Dynein Light Intermediate Chains Exhibit Different Arginine Methylation Patterns.Journal of clinical laboratory analysis · 2024Article
- TRIM21 reduces H1N1-induced inflammation and apoptosis by regulating the TBK1-IRF3 signaling pathway in A549 cells.Archives of virology · 2024Article
- Cleavage of HDAC6 to dampen its antiviral activity by nsp5 is a common strategy of swine enteric coronaviruses.Journal of virology · 2024Article
- Roles of TRIM21/Ro52 in connective tissue disease-associated interstitial lung diseases.Frontiers in immunology · 2024Review
- HDAC6 deacetylates IDH1 to promote the homeostasis of hematopoietic stem and progenitor cells.EMBO reports · 2023Article
- Multiple Roles of TRIM21 in Virus Infection.International journal of molecular sciences · 2023Review
- Histone deacetylase 6's function in viral infection, innate immunity, and disease: latest advances.Frontiers in immunology · 2023Review
- Functional skewing of TRIM21-SIRT5 interplay dictates IL-1β production in DSS-induced colitis.EMBO reports · 2022Article
- The emerging roles of TRIM21 in coordinating cancer metabolism, immunity and cancer treatment.Frontiers in immunology · 2022Review
- USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B-cell lymphoma.Journal of clinical laboratory analysis · 2021Article
- Article
- TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease.Frontiers in immunology · 2021Review
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
Tripartite motif-containing protein 21 (TRIM21) is a cytosolic antibody receptor that targets the internalized virus-antibody complex to the proteasome for degradation. However, the precise mechanism regulating TRIM21 activity is unknown. Here we show that TRIM21 is a substrate of histone deacetylase 6 (HDAC6) and that its function is regulated by acetylation. HDAC6 interacts with TRIM21 through its PRYSPRY motif and deacetylates TRIM21 at lysine 385 and lysine 387, thus promoting its homodimerization. Inhibiting HDAC6 activity increases TRIM21 acetylation, and hyperacetylation blocks TRIM21 dimerization and ubiquitination, preventing its binding to the virus-antibody complex and its degradation via the ubiquitin-proteasome pathway. HDAC6 depletion or inhibition increases virus accumulation in cells, indicative of an impaired capacity for antibody-dependent intracellular neutralization of viruses, whereas TRIM21 acetylation-deficient K385/387R mutant rescues HDAC6 depletion-caused ADIN impairment. These findings provide evidence for HDAC6 as a novel regulator of TRIM21-mediated intracellular innate immunity.
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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.