Regulation of disease signaling by YOD1: potential implications for therapeutic strategies

Abstract 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: t...

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Main Authors: Jiawei Zhao, Xiaotong Guo, Houzhong Li, Yujing Chen, Jingjing Du, Juzheng Zhang, Jinfeng Gan, Peitao Wu, Siqi Chen, Xinwen Zhang, Jinfeng Yang, Jiamin Jin
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Cancer Cell International
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Online Access:https://doi.org/10.1186/s12935-025-03881-0
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author Jiawei Zhao
Xiaotong Guo
Houzhong Li
Yujing Chen
Jingjing Du
Juzheng Zhang
Jinfeng Gan
Peitao Wu
Siqi Chen
Xinwen Zhang
Jinfeng Yang
Jiamin Jin
author_facet Jiawei Zhao
Xiaotong Guo
Houzhong Li
Yujing Chen
Jingjing Du
Juzheng Zhang
Jinfeng Gan
Peitao Wu
Siqi Chen
Xinwen Zhang
Jinfeng Yang
Jiamin Jin
author_sort Jiawei Zhao
collection DOAJ
description Abstract 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.
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series Cancer Cell International
spelling doaj-art-6197d9ea10724e1da2946ce6bab98bf22025-08-20T03:27:18ZengBMCCancer Cell International1475-28672025-06-0125112110.1186/s12935-025-03881-0Regulation of disease signaling by YOD1: potential implications for therapeutic strategiesJiawei Zhao0Xiaotong Guo1Houzhong Li2Yujing Chen3Jingjing Du4Juzheng Zhang5Jinfeng Gan6Peitao Wu7Siqi Chen8Xinwen Zhang9Jinfeng Yang10Jiamin Jin11Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityKey Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical UniversityAbstract 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.https://doi.org/10.1186/s12935-025-03881-0DeubiquitinasesYOD1Signaling pathwaysDiseaseInhibitor
spellingShingle Jiawei Zhao
Xiaotong Guo
Houzhong Li
Yujing Chen
Jingjing Du
Juzheng Zhang
Jinfeng Gan
Peitao Wu
Siqi Chen
Xinwen Zhang
Jinfeng Yang
Jiamin Jin
Regulation of disease signaling by YOD1: potential implications for therapeutic strategies
Cancer Cell International
Deubiquitinases
YOD1
Signaling pathways
Disease
Inhibitor
title Regulation of disease signaling by YOD1: potential implications for therapeutic strategies
title_full Regulation of disease signaling by YOD1: potential implications for therapeutic strategies
title_fullStr Regulation of disease signaling by YOD1: potential implications for therapeutic strategies
title_full_unstemmed Regulation of disease signaling by YOD1: potential implications for therapeutic strategies
title_short Regulation of disease signaling by YOD1: potential implications for therapeutic strategies
title_sort regulation of disease signaling by yod1 potential implications for therapeutic strategies
topic Deubiquitinases
YOD1
Signaling pathways
Disease
Inhibitor
url https://doi.org/10.1186/s12935-025-03881-0
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