{"title":"OTU deubiquitinases in disease: roles and targeting.","authors":"Yu Deng, Pengda Liu","doi":"10.1016/j.molmed.2025.05.006","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8000,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in molecular medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.molmed.2025.05.006","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍：
Trends in Molecular Medicine (TMM) aims to offer concise and contextualized perspectives on the latest research advancing biomedical science toward better diagnosis, treatment, and prevention of human diseases. It focuses on research at the intersection of basic biology and clinical research, covering new concepts in human biology and pathology with clear implications for diagnostics and therapy. TMM reviews bridge the gap between bench and bedside, discussing research from preclinical studies to patient-enrolled trials. The major themes include disease mechanisms, tools and technologies, diagnostics, and therapeutics, with a preference for articles relevant to multiple themes. TMM serves as a platform for discussion, pushing traditional boundaries and fostering collaboration between scientists and clinicians. The journal seeks to publish provocative and authoritative articles that are also accessible to a broad audience, inspiring new directions in molecular medicine to enhance human health.
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