{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRIM69 functions as a potent antiviral effector induced by interferon responses. It restricts Dengue virus replication by binding directly to the viral nonstructural protein NS3, mediating its polyubiquitination and subsequent degradation (via lysine 104), thereby suppressing viral replication. In addition, TRIM69 potently blocks vesicular stomatitis Indiana virus infection – with sensitivity determined by minimal viral sequence changes – and exhibits a broader antiflaviviral activity through direct interactions with viral protease components. Its antiviral actions also extend to the inhibition of HIV-1 (as well as HIV-2 and SIVMAC) infection in interferon‐stimulated myeloid cells via the modulation of microtubule stability (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its antiviral role, TRIM69 acts as an E3 ubiquitin ligase that regulates the stability of specific proteins in diverse biological contexts. Early work in murine testis identified a testis‐specific TRIM protein (Trif) containing a RING finger, B‐box, and B30.2 domain suggestive of roles in spermatogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ", while in human testis, TRIM69 was demonstrated to mediate substrate ubiquitination in an E2 enzyme–selective manner requiring an intact RING domain."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In human lens epithelial cells, TRIM69 interacts with p53 and promotes its ubiquitination, a process that suppresses UVB-induced reactive oxygen species generation and apoptosis, with Foxo3a identified as a transcriptional regulator of TRIM69 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond antiviral defense and protein quality control in developmental contexts, TRIM69 influences cancer-related processes and mitotic regulation. In hepatocellular carcinoma, TRIM69 mediates the polyubiquitination and degradation of the ferroptosis suppressor protein FSP1 – a mechanism that is competitively blocked by the long noncoding RNA lncFAL, thereby altering ferroptosis vulnerability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Furthermore, in gastric cancer, TRIM69 suppresses anoikis resistance and metastasis by interacting with PRKCD to catalyze its K48-linked polyubiquitination, which in turn modulates the production of neurotrophins such as BDNF."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In parallel, TRIM69 regulates centrosome dynamics by binding to MST2, enhancing its association with PLK1, and promoting microtubule bundling to ensure proper centrosome disjunction and bipolar mitosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kezhen Wang, Chunling Zou, Xiujuan Wang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mapping of molecular interactions between human E3 ligase TRIM69 and Dengue virus NS3 protease using hydrogen-deuterium exchange mass spectrometry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-022-04245-x"}], "href": "https://doi.org/10.1007/s00018-022-04245-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35397701"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35397701"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuxin Song, Xuan-Nhi Nguyen, Anuj Kumar, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A novel member of the RBCC family, Trif, expressed specifically in the spermatids of mouse testis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mech Dev (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0925-4773(01)00485-3"}], "href": "https://doi.org/10.1016/s0925-4773(01"}, {"type": "t", "text": "00485-3) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11578878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11578878"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yongqing Han, Rong Li, Jinlan Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterisation of human RING finger protein TRIM69, a novel testis E3 ubiquitin ligase and its subcellular localisation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2012.10.109"}], "href": "https://doi.org/10.1016/j.bbrc.2012.10.109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23131556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23131556"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xianfang Rong, Jun Rao, Dan Li, et al. 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