疾病中的OTU去泛素化酶：作用与靶向
OTU deubiquitinases in disease: roles and targeting.
作者信息
Deng Yu, Liu Pengda
机构信息
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
出版信息
Trends Mol Med. 2025 Jun 16. doi: 10.1016/j.molmed.2025.05.006.
Dysregulation of protein homeostasis contributes to many human diseases and is an emerging therapeutic target. Proteasome-mediated degradation requires ubiquitin tagging, a process regulated by E3 ligases and reversed by deubiquitinases (DUBs). Among DUBs, the ovarian tumor protease (OTU) family exhibits poly-ubiquitin linkage-specific activity and regulates diverse cellular processes. OTU dysregulation has been linked to diseases such as cancer, highlighting their potential as drug targets. This review summarizes current knowledge of OTU functions, regulatory mechanisms, and disease associations, as well as therapeutic strategies targeting OTUs. By examining these aspects, we aim to provide insights into the pathophysiological roles of OTUs and support ongoing efforts to develop OTU-targeted therapies for human diseases.
蛋白质稳态失调与许多人类疾病相关，是一个新兴的治疗靶点。蛋白酶体介导的降解需要泛素标记，这一过程由E3连接酶调节，并由去泛素化酶（DUBs）逆转。在DUBs中，卵巢肿瘤蛋白酶（OTU）家族具有多聚泛素连接特异性活性，并调节多种细胞过程。OTU失调与癌症等疾病有关，凸显了它们作为药物靶点的潜力。本综述总结了目前关于OTU功能、调节机制、疾病关联以及针对OTU的治疗策略的知识。通过研究这些方面，我们旨在深入了解OTU的病理生理作用，并支持目前为人类疾病开发OTU靶向疗法的努力。
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