{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRIM21 is a unique intracellular receptor for IgG that functions as a cytosolic antibody sensor, binding with exceptionally high affinity to the Fc portion of antibodies attached to invading viruses. Upon viral entry, TRIM21 is rapidly recruited to antibody–virus complexes and, through its RING‐domain E3 ubiquitin ligase activity, it marks these complexes for proteasomal degradation, thereby neutralizing infection at a post‐entry stage. This direct mechanism of intracellular neutralization has been demonstrated across multiple studies, emphasizing its role as a last‐line defence in antiviral immunity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its direct antiviral action, TRIM21 has been shown to intricately regulate innate immune signalling. It modulates key transcription factors such as interferon regulatory factor 3 (IRF3) and IRF7, sometimes targeting them for proteasomal degradation to dampen type I interferon responses and, in other contexts, interfering with their degradation to prolong antiviral gene transcription. Moreover, TRIM21 contributes to MAVS-dependent signalling through K27-linked polyubiquitination that promotes TBK1 recruitment and subsequent cytokine production. These findings underscore a dual role in fine-tuning inflammatory responses via its E3 ligase activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond virus neutralization and cytokine regulation, TRIM21 participates in broader intracellular homeostatic mechanisms. It acts as a selective autophagy receptor by binding specific targets such as IRF3, and it mediates redox regulation through direct interaction with proteins like SQSTM1/p62—thereby modulating p62 oligomerization and consequently the antioxidant response. Furthermore, in the context of tumor suppressor control, TRIM21 has been implicated in modulating the stability of key regulatory proteins such as GMPS, with downstream effects on p53, and it participates in T cell signalling via its impact on activation-induced cytokine production. Such functions highlight TRIM21’s versatile role in controlling diverse cellular pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, dysregulation of TRIM21 is associated with autoimmunity and cancer. Elevated expression and autoantibody targeting of TRIM21 (also known as Ro52) occur in systemic autoimmune conditions such as Sjögren’s syndrome and systemic sclerosis, implicating its altered function in disease pathogenesis. In some settings, aberrant TRIM21 activity may contribute to defective clearance of apoptotic cells and abnormal cytokine production, thereby influencing autoimmune responses. Additionally, TRIM21’s role in modulating cell proliferation, apoptosis and even the sensitivity of tumours to therapies such as radiotherapy underscores its emerging significance as a biomarker and potential therapeutic target in several cancers. These clinical associations and regulatory functions have been demonstrated in a range of studies addressing genetic screening, autoantibody profiles, and tumour suppressor mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "34"}, {"type": "fg_f", "ref": "28"}, {"type": "fg_f", "ref": "35"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Donna L Mallery, William A McEwan, Susanna R Bidgood, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Self protection from anti-viral responses--Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-Like receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0011776"}], "href": "https://doi.org/10.1371/journal.pone.0011776"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20668674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20668674"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Binbin Xue, Huiyi Li, Mengmeng Guo, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201503023"}], "href": "https://doi.org/10.1083/jcb.201503023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26347139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26347139"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Ji-An Pan, Yu Sun, Ya-Ping Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM21 Ubiquitylates SQSTM1/p62 and Suppresses Protein Sequestration to Regulate Redox Homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2016.02.007"}], "href": "https://doi.org/10.1016/j.molcel.2016.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26942676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26942676"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "B Ashok Reddy, Jan A van der Knaap, Alice G M Bot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nucleotide biosynthetic enzyme GMP synthase is a TRIM21-controlled relay of p53 stabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2013.12.017"}], "href": "https://doi.org/10.1016/j.molcel.2013.12.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24462112"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24462112"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Tomonori Ishii, Kei Ohnuma, Akikazu Murakami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SS-A/Ro52, an autoantigen involved in CD28-mediated IL-2 production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.170.7.3653"}], "href": "https://doi.org/10.4049/jimmunol.170.7.3653"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646630"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Keiji Wada, Tetsu Kamitani "}, {"type": "b", "children": [{"type": "t", "text": "UnpEL/Usp4 is ubiquitinated by Ro52 and deubiquitinated by itself."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.01.144"}], "href": "https://doi.org/10.1016/j.bbrc.2006.01.144"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16472766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16472766"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Alexander Espinosa, Wei Zhou, Monica Ek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Sjogren's syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.176.10.6277"}], "href": "https://doi.org/10.4049/jimmunol.176.10.6277"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16670339"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16670339"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Robert M Clancy, Petra J Neufing, Ping Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired clearance of apoptotic cardiocytes is linked to anti-SSA/Ro and -SSB/La antibodies in the pathogenesis of congenital heart block."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI27803"}], "href": "https://doi.org/10.1172/JCI27803"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16906225"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16906225"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "William A McEwan, Benjamin Falcon, Marina Vaysburd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1607215114"}], "href": "https://doi.org/10.1073/pnas.1607215114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28049840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28049840"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Marie Hudson, Janet Pope, Michael Mahler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clinical significance of antibodies to Ro52/TRIM21 in systemic sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Res Ther (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/ar3763"}], "href": "https://doi.org/10.1186/ar3763"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22394602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22394602"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Linn Strandberg, Aurelie Ambrosi, Alexander Espinosa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interferon-alpha induces up-regulation and nuclear translocation of the Ro52 autoantigen as detected by a panel of novel Ro52-specific monoclonal antibodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10875-007-9157-0"}], "href": "https://doi.org/10.1007/s10875-007-9157-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18071879"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18071879"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Keiji Wada, Tetsu Kamitani "}, {"type": "b", "children": [{"type": "t", "text": "Autoantigen Ro52 is an E3 ubiquitin ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2005.11.029"}], "href": "https://doi.org/10.1016/j.bbrc.2005.11.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16297862"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16297862"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "S Katsiougiannis, R Tenta, F N Skopouli "}, {"type": "b", "children": [{"type": "t", "text": "Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular redistribution of the autoantigens Ro/Sjögren's syndrome-related antigen A (SSA) and La/SSB in salivary gland epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cei.12638"}], "href": "https://doi.org/10.1111/cei.12638"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25845745"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25845745"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Zhaolong Li, Chen Huan, Hong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM21-mediated proteasomal degradation of SAMHD1 regulates its antiviral activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201847528"}], "href": "https://doi.org/10.15252/embr.201847528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31797533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31797533"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Fang Wang, Ye Zhang, Jianliang Shen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Ubiquitin E3 Ligase TRIM21 Promotes Hepatocarcinogenesis by Suppressing the p62-Keap1-Nrf2 Antioxidant Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Gastroenterol Hepatol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jcmgh.2021.01.007"}], "href": "https://doi.org/10.1016/j.jcmgh.2021.01.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33482392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33482392"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Soledad Retamozo, Miriam Akasbi, Pilar Brito-Zerón, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anti-Ro52 antibody testing influences the classification and clinical characterisation of primary Sjögren's syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Rheumatol (2012)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22704838"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22704838"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "B Nakken, R Jonsson, A I Bolstad "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms of the Ro52 gene associated with anti-Ro 52-kd autoantibodies in patients with primary Sjögren's syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1529-0131(200103)44:3"}, {"type": "a", "children": [{"type": "t", "text": "638::AID-ANR112"}], "href": "638::AID-ANR112"}, {"type": "t", "text": "3.0.CO;2-J"}], "href": "https://doi.org/10.1002/1529-0131(200103"}, {"type": "t", "text": "44:3"}, {"type": "a", "children": [{"type": "t", "text": "638::AID-ANR112"}], "href": "638::AID-ANR112"}, {"type": "t", "text": "3.0.CO;2-J) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11263778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11263778"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Guangxi Zhou, Wei Wu, Lin Yu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tripartite motif-containing (TRIM) 21 negatively regulates intestinal mucosal inflammation through inhibiting T"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "H"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "1/T"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "H"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "17 cell differentiation in patients with inflammatory bowel diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2017.09.038"}], "href": "https://doi.org/10.1016/j.jaci.2017.09.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29113905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29113905"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Xintian Chen, Zhongwei Li, Hongmei Yong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Trim21-mediated HIF-1α degradation attenuates aerobic glycolysis to inhibit renal cancer tumorigenesis and metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2021.03.023"}], "href": "https://doi.org/10.1016/j.canlet.2021.03.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33794309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33794309"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Michael Wodkowski, Marie Hudson, Susanna Proudman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Monospecific anti-Ro52/TRIM21 antibodies in a tri-nation cohort of 1574 systemic sclerosis subjects: evidence of an association with interstitial lung disease and worse survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Rheumatol (2015)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26315678"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26315678"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Jun-Yan Li, Yin Zhao, Sha Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-023-36523-y"}], "href": "https://doi.org/10.1038/s41467-023-36523-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36797289"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36797289"}]}]}]}