Zhao Jiawei, Guo Xiaotong, Li Houzhong, Chen Yujing, Du Jingjing, Zhang Juzheng, Gan Jinfeng, Wu Peitao, Chen Siqi, Zhang Xinwen, Yang Jinfeng, Jin Jiamin
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, 541199, Guangxi, China.
Guangxi Health Commission Key Laboratory of Tumor Immunology and Receptor- Targeted Drug Basic Research, Guilin Medical University, Guilin, Guangxi, China.
Cancer Cell Int. 2025 Jun 24;25(1):232. doi: 10.1186/s12935-025-03881-0.
YOD1 (OTUD2) is a pivotal deubiquitinating enzyme (DUB) of the Otubain family. It plays an essential role in protein degradation and the regulation of cell signal transduction, influencing various biological processes. The activity of YOD1 is mediated through its three structural domains: the Ubiquitin Regulatory X (UBX) domain, the Zinc Finger (ZNF) domain, and the Ovarian Tumor (OTU) domain. Specifically, the UBX domain regulates protein interactions, mitochondrial quality control, and immune responses. The ZNF domain facilitates protein localization, degradation, and cancer progression. The OTU domain drives deubiquitination, ensuring protein stability and regulating key signaling pathways. In recent years, increasing attention has been paid to the role of YOD1 in various diseases. Studies have demonstrated that YOD1 influences critical cellular activities such as proliferation, apoptosis, migration, and invasion by modulating key signaling pathways, including Hippo and TGF-β. Abnormal YOD1 expression is closely linked to the development of several cancers, including breast, liver, and lung cancer. Moreover, in non-malignant conditions such as inflammation and vascular diseases, YOD1 plays a key role in maintaining tissue homeostasis and repairing damaged tissues. Given its multifaceted roles in both tumorigenic and non-tumorigenic contexts, YOD1 is considered a promising target for therapeutic strategies. This review systematically analyzes the key signaling pathways regulated by YOD1, with a focus on elucidating its potential therapeutic value in cancer and various non-tumor diseases. Additionally, it provides a comprehensive review of the recent research progress in the field of YOD1 inhibitors. Our aim is to underscore the significance of YOD1 as a potential therapeutic target, to provide a theoretical basis for the development of innovative therapeutic strategies, and to offer new perspectives and insights for future related research.
YOD1（OTUD2）是奥图巴因家族的一种关键去泛素化酶（DUB）。它在蛋白质降解和细胞信号转导调节中发挥着重要作用，影响着各种生物学过程。YOD1的活性通过其三个结构域介导：泛素调节X（UBX）结构域、锌指（ZNF）结构域和卵巢肿瘤（OTU）结构域。具体而言，UBX结构域调节蛋白质相互作用、线粒体质量控制和免疫反应。ZNF结构域促进蛋白质定位、降解和癌症进展。OTU结构域驱动去泛素化，确保蛋白质稳定性并调节关键信号通路。近年来，YOD1在各种疾病中的作用受到越来越多的关注。研究表明，YOD1通过调节关键信号通路，如Hippo和TGF-β，影响细胞增殖、凋亡、迁移和侵袭等关键细胞活动。YOD1表达异常与包括乳腺癌、肝癌和肺癌在内的多种癌症的发生密切相关。此外，在炎症和血管疾病等非恶性疾病中，YOD1在维持组织稳态和修复受损组织中起关键作用。鉴于其在致瘤和非致瘤环境中的多方面作用，YOD1被认为是治疗策略的一个有前景的靶点。本综述系统分析了YOD1调节的关键信号通路，重点阐明其在癌症和各种非肿瘤疾病中的潜在治疗价值。此外，它还全面综述了YOD1抑制剂领域的最新研究进展。我们的目的是强调YOD1作为潜在治疗靶点的重要性，为创新治疗策略的开发提供理论基础，并为未来相关研究提供新的视角和见解。
