{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTRIM17 is a member of the TRIM family that exhibits E3 ubiquitin ligase activity and plays a key role in controlling cell proliferation by targeting specific substrates. For example, TRIM17 (originally termed Terf) directly interacts with the kinetochore component ZWINT and promotes its degradation, thereby negatively regulating cell division and growth."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n\nTRIM17’s own stability is tightly regulated through its interaction with other TRIM proteins. It undergoes auto‐ubiquitination leading to proteasomal degradation; however, binding to TRIM44 can inhibit its ubiquitination and thereby stabilize TRIM17, suggesting a complex self‐regulatory mechanism within the TRIM family."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n\nIn addition, TRIM17 modulates the stability of key apoptosis and cell survival regulators. In one context, TRIM17 blocks the association of the E3 ubiquitin ligase TRIM28 with the anti‐apoptotic protein BCL2A1, resulting in its stabilization and thereby influencing cell survival pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n\nMoreover, TRIM17 has been implicated in the regulation of neuronal apoptosis. It preferentially binds to SUMOylated forms of the transcription factor NFATc3, reducing its calcium-mediated nuclear translocation and transcriptional activity. This modulation creates a bias in NFAT signaling that contributes to neuronal cell death, and it may be further reinforced by a feedback loop wherein NFATc3 regulates TRIM17 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n\nTRIM17 also functions as an important regulator of selective autophagy. It exerts dual actions by stabilizing Mcl-1 in complexes with Beclin-1, thereby dampening autophagic degradation of selected substrates, while in other contexts it facilitates the removal of midbody remnants by allowing the dissociation of the Mcl-1–Beclin-1 complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n\nWithin neuronal systems, TRIM17 influences the regulation of alpha-synuclein expression by modulating the degradation of the transcription factor ZSCAN21. Specifically, TRIM17 counteracts the TRIM41-mediated ubiquitination of ZSCAN21, leading to its stabilization—a process that is linked to modulation of SNCA transcription, with significant implications for the pathogenesis of Parkinson’s disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n\nFinally, in the context of oncology, TRIM17 is upregulated in cisplatin-resistant non-small cell lung cancer cells. Its overexpression facilitates chemoresistance by promoting the K48-linked ubiquitination and subsequent degradation of RBM38, which in turn attenuates the production of reactive oxygen species and DNA damage, thereby helping tumor cells survive cisplatin treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hiroshi Endo, Kazuhiro Ikeda, Tomohiko Urano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Terf/TRIM17 stimulates degradation of kinetochore protein ZWINT and regulates cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvr128"}], "href": "https://doi.org/10.1093/jb/mvr128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22023800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22023800"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Tomohiko Urano, Takahiko Usui, Shizu Takeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM44 interacts with and stabilizes terf, a TRIM ubiquitin E3 ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.04.010"}], "href": "https://doi.org/10.1016/j.bbrc.2009.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19358823"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19358823"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Loïc Lionnard, Pauline Duc, Margs S Brennan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM17 and TRIM28 antagonistically regulate the ubiquitination and anti-apoptotic activity of BCL2A1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-018-0169-5"}], "href": "https://doi.org/10.1038/s41418-018-0169-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30042493"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30042493"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "B Mojsa, S Mora, J P Bossowski, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "TRIM17 contributes to autophagy of midbodies while actively sparing other targets from degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.190017"}], "href": "https://doi.org/10.1242/jcs.190017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27562068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27562068"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Iréna Lassot, Stéphan Mora, Suzanne Lesage, et al. 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