{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRIM56 is an interferon‐inducible protein that functions primarily as an E3 ubiquitin ligase, serving as a pivotal regulator of innate immune signaling. It enhances type I interferon responses by modifying key intracellular sensors: for example, TRIM56 mediates lysine 63‐linked ubiquitination of STING in response to cytosolic double‐stranded DNA, and it directly monoubiquitinates cGAS at Lys335 to promote its dimerization and DNA binding, thereby amplifying cGAMP production. Moreover, TRIM56 positively regulates the Toll‐like receptor 3 (TLR3) pathway through its interaction with the adaptor protein TRIF, a process also influenced by its phosphorylation at specific serine residues that are critical for proper IRF3 and NF‑κB activation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in immune signaling, TRIM56 acts as a versatile antiviral effector by employing distinct mechanisms against a broad spectrum of viruses. It restricts positive‐strand RNA viruses—including flaviviruses such as yellow fever virus, dengue virus, and human coronaviruses—by interfering with intracellular viral RNA synthesis, and it binds directly to viral RNA in the case of Zika virus, thereby inhibiting replication. Furthermore, TRIM56 facilitates the ubiquitination and proteasomal degradation of viral proteins, exemplified by its targeting of the RNA‐dependent RNA polymerase of coxsackievirus B. The importance of TRIM56 is underscored by its interception by bacterial effectors such as SopA, which target its E3 ligase activity to undermine host antiviral defenses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates TRIM56 in the regulation of tumorigenesis and cancer progression. In ovarian cancer cells, TRIM56 targets vimentin for ubiquitination and degradation, thereby modulating epithelial-to-mesenchymal transition and metastatic potential; dysregulation of its expression correlates with enhanced migration and invasion. Altered TRIM56 levels have further been linked to adverse clinical outcomes in multiple malignancies, including hepatocellular carcinoma, glioblastoma/glioma, and non‑small cell lung cancer. In lung cancer specifically, TRIM56 influences cancer stem cell phenotypes and chemoresistance by modulating the ubiquitination of the aryl hydrocarbon receptor. Additionally, preliminary studies in multiple myeloma suggest a role for TRIM56 in tumor biology, underscoring its potential as both a prognostic biomarker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings reveal that TRIM56 operates as a multifunctional protein at the intersection of innate antiviral defense and oncogenic regulation. Its ability to regulate key signaling pathways through targeted ubiquitination, to directly restrict viral infection, and to influence tumor cell behavior highlights TRIM56 as a critical mediator of both host immunity and cancer progression. Continued investigation into its molecular determinants and interaction networks promises to advance novel therapeutic strategies in combating viral infections and malignancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tetsuo Tsuchida, Jian Zou, Tatsuya Saitoh, et al. 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