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

Abstract

YOD1, also known as OTUD2, is a critical member of the Otubain family of deubiquitinating enzymes (DUBs), playing a central role in the regulation of protein degradation and cellular signal transduction. Through its action on the ubiquitin-proteasome system, YOD1 influences a range of essential biological processes. Its functional activity is mediated by three key structural domains: the Ubiquitin Regulatory X (UBX) domain, the Zinc Finger (ZNF) domain, and the Ovarian Tumor (OTU) domain, each contributing uniquely to its cellular functions. The UBX domain is involved in the regulation of protein-protein interactions, mitochondrial quality control, and immune responses. The ZNF domain governs subcellular localization and protein turnover and is implicated in cancer progression. The OTU domain is responsible for catalytic deubiquitination activity, maintaining protein stability and modulating vital signaling cascades.

In recent years, considerable progress has been made in understanding the role of YOD1 in human health and disease. Evidence has increasingly shown that YOD1 exerts a profound impact on critical cellular behaviors such as proliferation, apoptosis, migration, and invasion by modulating pivotal pathways including the Hippo and TGF-β signaling pathways. Dysregulation of YOD1 expression has been closely associated with the pathogenesis of various malignancies, including cancers of the breast, liver, and lung. Beyond its role in oncogenesis, YOD1 has also been identified as a crucial regulator in non-cancerous conditions such as chronic inflammation, vascular dysfunction, and tissue injury repair, where it contributes to maintaining tissue integrity and promoting recovery.

Given its wide-ranging effects in both malignant and non-malignant contexts, YOD1 has emerged as a compelling target for therapeutic intervention. This review presents a systematic analysis of the major signaling pathways governed by YOD1, with particular emphasis on its potential applications in the treatment of cancer and other diseases. Moreover, it examines recent advances in the development of small-molecule inhibitors targeting YOD1, highlighting their potential in preclinical and therapeutic settings. XL177A By consolidating current knowledge and research findings, this review aims to emphasize the biological and clinical relevance of YOD1, offering a solid theoretical framework for future drug development and novel therapeutic strategies. It also seeks to provide fresh insights into the direction of future investigations focused on the modulation of deubiquitination mechanisms for disease treatment.

Keywords: deubiquitinases, disease, inhibitor, signaling pathways, YOD1

Conflict of interest statement
The authors declare no competing interests. The use of generative AI or AI-assisted technologies was not applicable in the writing of this manuscript.