{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRIM7, a member of the tripartite motif (TRIM) family of E3 ubiquitin ligases, plays multifaceted roles in cellular metabolism and cancer. Alternative splice isoforms of the GNIP gene, which give rise to TRIM7 and related proteins, interact with glycogenin to stimulate its self‐glucosylation and may thereby participate in the initiation of glycogen synthesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In the context of tumorigenesis, TRIM7 has been shown to exhibit dual and context‐dependent functions. In hepatocellular carcinoma, for example, overexpression of TRIM7 promotes cell proliferation and cell-cycle progression by enhancing p38 activation via the ubiquitination and degradation of DUSP6 (thereby acting in an oncogenic manner)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " By contrast, in several other cancers including liver, lung, renal, and gastric carcinomas, TRIM7 targets oncogenic substrates such as Src and the NF‑κB subunit p65 for ubiquitination and proteasomal degradation, thus suppressing malignant progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": " Moreover, TRIM7 upregulation has been associated with advanced carotid atherosclerosis through activation of the c‑Jun/AP‑1 signaling pathway in vascular smooth muscle cells, and its role in osteosarcoma remains an open question."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its functions in metabolism and cancer, TRIM7 is emerging as a key modulator of innate antiviral immunity. Structural and functional studies have revealed that the C‑terminal B30.2 domain of TRIM7 mediates specific recognition of viral proteins bearing a C‑terminal glutamine residue, marking them for Lys48‑linked polyubiquitination and subsequent proteasomal degradation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Furthermore, during encephalomyocarditis virus infection, TRIM7 positively regulates type I interferon signals by engaging components of the RIG‑I/MDA5/MAVS pathway to suppress viral replication."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent investigations have further broadened the spectrum of TRIM7’s biological impact. In glioblastoma, ongoing studies are deciphering TRIM7’s role in the regulation of ferroptosis, which may contribute to tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In non‑small cell lung cancer, TRIM7 (or its isoform GNIP1) has been implicated in the modulation of autophagy pathways"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", while altered expression of TRIM7 in peripheral blood mononuclear cells has recently been explored for its potential diagnostic value in sepsis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " Collectively, these findings underscore TRIM7 as a multifaceted regulator whose diverse functions in metabolism, cell proliferation, antiviral defense, and inflammation may offer novel avenues for therapeutic intervention.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexander V Skurat, Amy D Dietrich, Lanmin Zhai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GNIP, a novel protein that binds and activates glycogenin, the self-glucosylating initiator of glycogen biosynthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M201190200"}], "href": "https://doi.org/10.1074/jbc.M201190200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11916970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11916970"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Marta Montori-Grau, Robert Pedreira-Casahuga, Zoé Boyer-Díaz, et al. 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