{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRIM38 is a member of the tripartite motif (TRIM) protein family that possesses a conserved RING, B-box, coiled-coil, and SPRY domain, typical of proteins involved in ubiquitination and diverse cellular processes. Despite initial gaps in understanding its precise functions, recent studies have begun to delineate its multifaceted roles, particularly in modulating immune signaling pathways and inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of innate immunity, TRIM38 functions as a negative regulator by targeting critical adaptors. For example, it inhibits Toll-like receptor 3 (TLR3)-mediated type I interferon production via K48-linked ubiquitination and proteasomal degradation of TRIF, thereby curbing excessive antiviral signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTRIM38 further modulates inflammatory responses in disease settings. In rheumatoid arthritis, it is recruited through interactions facilitated by NLRP6 to promote lysosome-dependent degradation of transforming growth factor-β-activated kinase 1-binding proteins 2/3, leading to dampened NF-κB activation and reduced production of pro-inflammatory cytokines. Similarly, in nonalcoholic fatty liver disease, decreased expression of TRIM38 correlates with exacerbated hepatic steatosis, inflammation, and fibrosis, while its overexpression ameliorates these features by interfering with MAPK pathway activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn antiviral defense, TRIM38 operates as an interferon-stimulated gene to restrict viral replication. Notably, in the context of hepatitis B virus infection, increased TRIM38 expression enhances the antiviral effects of IFN-α by promoting the expression of antiviral proteins, ultimately inhibiting HBV replication and gene expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also points to a role for TRIM38 in tumor biology. Although its implications in bladder cancer remain inconclusive, studies in non–small cell lung cancer reveal that TRIM38 exerts tumor suppressor functions by inhibiting cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition through modulation of the AMPK/NF-κB/NLRP3 signaling cascade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, TRIM38 plays a crucial role at the maternal-fetal interface by maintaining immune tolerance. Its ability to mediate K48-linked ubiquitination of MITA is higher in M2 macrophages, resulting in diminished expression of this pro-pyroptotic factor and reduced pyroptosis, which is essential for preserving the immunosuppressive microenvironment necessary for successful pregnancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xinlei Liu, Xiaobo Lei, Zhuo Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Enterovirus 71 induces degradation of TRIM38, a potential E3 ubiquitin ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virol J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1743-422X-8-61"}], "href": "https://doi.org/10.1186/1743-422X-8-61"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21306652"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21306652"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xin-lei Liu, Xiao-bo Lei, Jian-wei Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Identification A novel protein TRIM38 that activate NF-kappaB signaling pathways]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi (2011)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21789858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21789858"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Qinghua Xue, Zhuo Zhou, Xiaobo Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM38 negatively regulates TLR3-mediated IFN-β signaling by targeting TRIF for degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0046825"}], "href": "https://doi.org/10.1371/journal.pone.0046825"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23056470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23056470"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yang Lin, Zhengqiang Luo "}, {"type": "b", "children": [{"type": "t", "text": "NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast-like synoviocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.12622"}], "href": "https://doi.org/10.1002/1873-3468.12622"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28295271"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28295271"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xinxin Yao, Ruixiang Dong, Sha Hu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tripartite motif 38 alleviates the pathological process of NAFLD-NASH by promoting TAB2 degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jlr.2023.100382"}], "href": "https://doi.org/10.1016/j.jlr.2023.100382"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37116711"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37116711"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Haiying Luo, Xiaoxia Hu, Yadi Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The antiviral activity of tripartite motif protein 38 in hepatitis B virus replication and gene expression and its association with treatment responses during PEG-IFN-α antiviral therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virology (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.virol.2022.12.014"}], "href": "https://doi.org/10.1016/j.virol.2022.12.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36623352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36623352"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiaojing Wang, Hongchao He, Wenbin Rui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM38 triggers the uniquitination and degradation of glucose transporter type 1 (GLUT1) to restrict tumor progression in bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-021-03173-x"}], "href": "https://doi.org/10.1186/s12967-021-03173-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34906161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34906161"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kaihua Zhang, Guihu Lin, Zhenkai Nie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM38 suppresses migration, invasion, metastasis, and proliferation in non-small cell lung cancer (NSCLC) via regulating the AMPK/NF-κB/NLRP3 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biochem (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11010-023-04823-y"}], "href": "https://doi.org/10.1007/s11010-023-04823-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37566200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37566200"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Jun Liu, Yan Deng, An Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Investigation into the role of the MITA-TRIM38 interaction in regulating pyroptosis and maintaining immune tolerance at the maternal-fetal interface."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-06314-w"}], "href": "https://doi.org/10.1038/s41419-023-06314-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38012139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38012139"}]}]}]}