Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression

Liang Wu; Zili Zhou; Yang Yu; Can Cheng; Shuai Zhou; Yuan Yan; Bofan Yu; Yuwei Zhang; Zhengyi Liu

doi:10.1038/s41419-024-06526-8

Cell Death and Disease (Feb 2024)

Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression

Liang Wu,
Zili Zhou,
Yang Yu,
Can Cheng,
Shuai Zhou,
Yuan Yan,
Bofan Yu,
Yuwei Zhang,
Zhengyi Liu

Affiliations

Liang Wu: Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Zili Zhou: Department of Gastrointestinal Surgery, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Yang Yu: Department of Breast Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University
Can Cheng: Department of General Surgery, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China
Shuai Zhou: Translational Research Institute, Henan Provincial and Zhengzhou City Key Laboratory of Non-coding RNA and Cancer Metabolism, Henan International Join Laboratory of Non-coding RNA and Metabolism in Cancer, Henan Provincial People’s Hospital, Academy of Medical Sciences, Zhengzhou University
Yuan Yan: Department of Breast Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University
Bofan Yu: Department of Breast Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University
Yuwei Zhang: Key Laboratory of Stem Cell Differentiation & Modification, School of Clinical Medicine, Henan University
Zhengyi Liu: Department of Breast Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University

DOI: https://doi.org/10.1038/s41419-024-06526-8
Journal volume & issue: Vol. 15, no. 2
pp. 1 – 12

Abstract

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Abstract Yin Yang 1 (YY1) is a key transcription factor that has been implicated in the development of several malignancies. The stability of YY1 is regulated by the ubiquitin-proteasome system. The role of deubiquitinases (DUBs) and their impact on YY1 remain to be fully elucidated. In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1. Over-expressed OTUD3 inhibited YY1 degradation, thereby increasing YY1 protein levels, whereas OTUD3 knockdown or knockout promoted YY1 degradation, thereby decreasing the proliferation of colorectal cancer (CRC). Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1. In CRC tissues, elevated the expression level of OTUD3 and YY1 were significantly associated with poor prognostic outcomes. These findings suggest that the OTUD3-YY1 pathway has therapeutic potential in CRC, and OTUD3 plays a critical role in regulating YY1.

Published in Cell Death and Disease

ISSN: 2041-4889 (Online)
Publisher: Nature Publishing Group
Country of publisher: United Kingdom
LCC subjects: Science: Biology (General): Cytology
Website: http://www.nature.com/cddis/index.html

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