{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUSP47 participates in the regulation of innate immunity through multiple mechanisms. In macrophages, USP47—together with its close homolog USP7—facilitates assembly and activation of inflammasomes by modulating ASC oligomerization and the ubiquitination status of NLRP3, thereby promoting the secretion of pro‐inflammatory cytokines. In parallel, USP47 functions as a negative regulator of antiviral responses by removing K63‐linked polyubiquitin chains from TRAF proteins, which dampens type I interferon signaling, and it also plays a critical role in the metabolic programming and suppressive function of regulatory T cells via controlling m6A‐dependent c-Myc translation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its immunomodulatory roles, USP47 is instrumental in maintaining genome integrity. It deubiquitylates the key base excision repair polymerase, Pol β, thereby ensuring its stability and enabling efficient repair of DNA strand breaks. Biochemical characterizations reveal that recombinant USP47 acts as a cysteine protease capable of cleaving various ubiquitin linkages, which not only underpins its function in DNA repair but also suggests roles in neuronal development through the stabilization of proteins such as katanin-p60 that promote axonal growth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUSP47 also contributes to the regulation of cell adhesion and epithelial plasticity. In epithelial cells, its recruitment to adherens junctions by the kinesin KIFC3 helps prevent the ubiquitination and subsequent cleavage of E-cadherin, thereby stabilizing cell-cell contacts. In contrast, under hypoxic conditions or during epithelial-to-mesenchymal transition (EMT), USP47 becomes upregulated and deubiquitinates the EMT-inducing transcription factor Snail, which leads to the disassembly of adherens junctions and promotes cellular invasiveness."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, USP47 exerts oncogenic effects in a range of malignancies. Its expression is often upregulated by aberrant non-coding RNA networks—such as through the downregulation of miR-204-5p in gastric cancer, or via lncRNAs like LINC00668 in colorectal cancer and DSCAM-AS1 in osteosarcoma—resulting in enhanced cellular proliferation, survival and stemness. In chronic myelogenous leukemia, USP47 contributes to tyrosine kinase inhibitor resistance by stabilizing factors involved in DNA damage repair. Moreover, USP47 interacts with components of ubiquitin ligase complexes and with the p53 pathway to regulate cell growth and survival, underscoring its potential as a target for anticancer therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUSP47 additionally plays a vital role in modulating the Wnt/β-catenin signaling pathway. By deubiquitinating β-catenin directly and by opposing the action of the E3 ligase XIAP on the transcriptional repressor TLE, USP47 contributes to the stabilization of β-catenin and maintains the expression of Wnt target genes during development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pablo Palazón-Riquelme, Jonathan D Worboys, Jack Green, et al. 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