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TRIM24 in Human Cancers: A Dual-Function Oncoprotein, Regulatory Mechanisms, and Emerging Therapeutic Strategies
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DOI：10.1002/ijc.70565.png)
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Abstract
En 中文
The tripartite motif-containing protein 24 (TRIM24) functions as a pivotal epigenetic scaffold and E3 ubiquitin ligase, orchestrating tumorigenesis through context-dependent dual roles. While frequently amplified in cancers such as prostate and breast carcinoma—where it drives oncogenesis via Wnt/β-catenin and PI3K/AKT pathway activation—emerging evidence positions TRIM24 as a tumor suppressor in specific contexts, modulating retinoic acid signaling and macrophage polarization. This dichotomy is governed by intricate post-translational modifications (PTMs), including phosphorylation-dependent nucleocytoplasmic shuttling and SUMOylation, which dictate substrate specificity for targets ranging from p53 to VHL. Furthermore, TRIM24 operates within a complex non-coding RNA network (e.g., miRNA-511, lncRNA NCK1-AS1) that fine-tunes its oncogenic output. Clinically, aberrant TRIM24 expression correlates with poor prognosis and therapeutic resistance across multiple malignancies. Mechanistically, its unique PHD-Bromo dual-domain structure confers specific recognition of the noncanonical H3K4me0/H3K23ac histone signature, presenting a compelling therapeutic target. Current strategies, including PROTAC degraders and allosteric inhibitors targeting its bromodomain or downstream effectors (e.g., DNA-PKcs, AURKB), demonstrate significant preclinical efficacy. This review synthesizes the molecular circuitry of TRIM24, elucidates the determinants of its functional switch, and evaluates emerging precision medicine approaches to overcome resistance in TRIM24-addicted tumors.
Keywords:
cancer
E3 ubiquitin ligase
oncogene
therapeutic target
TRIM24
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