{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUSP17 is a multifunctional deubiquitinating enzyme that plays a critical role in regulating cell cycle progression and oncogenic signaling. It modulates the activation and subcellular trafficking of key GTPases (including Ras and RhoA) and stabilizes pivotal transcription factors (such as ELK‐1, c-Myc, and DEC1) by removing degradative ubiquitin chains. In doing so, USP17 influences the processing of proteins essential for proper signal transduction—via substrates like RCE1 isoform 2 and SDS3—and ensures timely cell cycle transitions, thereby impacting cellular proliferation and transformation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its cell‐intrinsic roles, USP17 critically modulates immune and inflammatory responses. By deubiquitinating and thereby stabilizing components such as RIG-I, MDA5, and the transcription factor RORγt, USP17 ensures robust type I interferon responses and promotes Th17 cell differentiation. Its activity on nuclear IL-33 further influences the transcription of inflammatory cytokines, highlighting USP17’s capacity to fine-tune both innate and adaptive immune signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, USP17 has emerged as an important modulator of receptor dynamics, cell migration, and metastatic potential across diverse pathological contexts. It regulates chemokine-induced cytoskeletal rearrangements and, through its effects on receptor ubiquitination (including that of EGFR and PDGFRβ), alters the timing and extent of receptor internalization and downstream STAT3 signaling. Furthermore, USP17 promotes epithelial–mesenchymal transition via stabilization of factors such as SMAD4 and contributes to the invasive behavior of cancers—including non–small cell lung cancer and osteosarcoma. Biochemical studies also reveal that USP17 is an exceptionally potent enzyme whose activity is critical not only for tumour progression and metastasis but also for vascular signaling events and emerging conditions such as preeclampsia and smoking-associated tissue alterations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michelle de la Vega, James F Burrows, Cheryl McFarlane, et al. 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