Chen Yujing, Zhang Jingyi, Yang Jinfeng, Zhao Jiawei, Guo Xiaotong, Zhang Juzheng, Gan Jinfeng, Zhao Weijia, Chen Siqi, Zhang Xinwen, Lin Yi, Jin Jiamin
School of Pharmacy, Guilin Medical University, Guangxi, 541199, Guilin, People's Republic of China.
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, Guangxi, China.
Discov Oncol. 2025 May 10;16(1):715. doi: 10.1007/s12672-025-02480-9.
The ubiquitin-proteasome system enables post-transcriptional protein modification and is a major pathway for the degradation of most of them in eukaryotic cells. Among these, the ubiquitin-specific protease (USP) family is the most extensively studied. As an important member of the USP family, ubiquitin-specific protease 39 (USP39) plays an essential role in RNA splicing and protein regulation. This review comprehensively summarizes the structural characteristics and molecular functions of USP39, emphasizing its pivotal role in the regulation of cellular processes. Dysregulation of USP39 is closely associated with the progression of various cancers through mechanisms such as immune evasion, modulation of oncogenic signaling pathways, and altered RNA splicing. These processes impact key aspects of cancer biology, including proliferation, metastasis, and therapy resistance, underscoring the broad implications of USP39 in tumor progression. Recent studies position USP39 as a promising target for cancer treatment. Future research should explore its upstream regulatory networks, develop small-molecule inhibitors, and evaluate its potential for precision oncology. This review integrates the latest insight into USP39, providing a foundation for its clinical application in cancer therapy.
泛素-蛋白酶体系统能够进行转录后蛋白质修饰，是真核细胞中大多数蛋白质降解的主要途径。其中，泛素特异性蛋白酶（USP）家族是研究最为广泛的。作为USP家族的重要成员，泛素特异性蛋白酶39（USP39）在RNA剪接和蛋白质调控中发挥着至关重要的作用。本综述全面总结了USP39的结构特征和分子功能，强调了其在细胞过程调控中的关键作用。USP39的失调通过免疫逃逸、致癌信号通路调节和RNA剪接改变等机制与多种癌症的进展密切相关。这些过程影响癌症生物学的关键方面，包括增殖、转移和治疗抗性，突出了USP39在肿瘤进展中的广泛影响。最近的研究将USP39定位为一个有前景的癌症治疗靶点。未来的研究应探索其上游调控网络，开发小分子抑制剂，并评估其在精准肿瘤学中的潜力。本综述整合了对USP39的最新见解，为其在癌症治疗中的临床应用提供了基础。
