Open Access

REVIEW

Deubiquitinating Enzyme OTUDs: Focus on Cancers and Antiviral Response

Lang Chen¹, Rui Dong¹, Xuan Huan^2,*

1 Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China
2 Department of Geriatric Medicine, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China

* Corresponding Author: Xuan Huan. Email:

(This article belongs to the Special Issue: Identification of potential targets and biomarkers for cancers and the exploration of novel molecular mechanisms of tumorigenesis and metastasis)

Oncology Research 2025, 33(10), 2833-2856. https://doi.org/10.32604/or.2025.063644

Received 20 January 2025; Accepted 27 June 2025; Issue published 26 September 2025

Abstract

Deubiquitinating enzymes (DUBs) are key enzymes capable of cleaving ubiquitin chains and synergizing with ubiquitination modifications to regulate the function of key proteins and maintain normal physiological functions. OTUDs are a key subfamily of the ovarian tumor protease (OTU) family, with important DUB activities, and include mainly OTUD1, OTUD2, OTUD3, OTUD4, OTUD5, OTUD6A, and OTUD6B. In recent years, research on OTUD proteins has been gradually emphasized, and their aberrant expression has demonstrated significant research value in many diseases, such as cancer, immune abnormalities, neurological disorders, and embryonic developmental abnormalities. Therefore, a comprehensive understanding of the regulatory mechanisms of OTUD proteins and their use as therapeutic targets for diseases is of great value. This article focuses on the role of individual OTUD proteins in cancer progression and antiviral response. Importantly, in the context of cancer, we elaborate on their deubiquitinated protein targets and summarize the signaling mechanisms by which they promote or inhibit cancer progression. In the future, targeting OTUD proteins may become a therapeutic direction for cancer, and this review may be useful for research related to OTUD proteins and cancer. At present, there is a lack of research on targeted inhibitors or activators of OTUDs. More in vivo and in vitro studies on OTUDs may contribute to the development of inhibitors or agonists targeting OTUDs. Of course, when conducting these studies, researchers also need to pay attention to the impact of OTUDs on the host’s antiviral immune response.

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Keywords

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