p53 inhibits OTUD5 transcription to promote GPX4 degradation and induce ferroptosis in gastric cancer

Junjing Zhang; Tongguan Tian; Xinxing Li; Kai Xu; Yao Lu; Xia Li; Xinyu Zhao; Ziyi Cui; Zhenxiang Wang; Yuefan Zhou; Yixin Xu; Hongchen Li; Yan Zhang; Yu Du; Lei Lv; Yanping Xu

doi:10.1002/ctm2.70271

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (3) : e70271 DOI: 10.1002/ctm2.70271

RESEARCH ARTICLE

p53 inhibits OTUD5 transcription to promote GPX4 degradation and induce ferroptosis in gastric cancer

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Abstract

	•OTUD5 mediates GPX4 deubiquitination to regulate its stability.
	•Deletion of OTUD5 promotes ferroptosis and inhibits tumor growth.
	•Wild type p53 inhibits OTUD5 transcription, thereby promoting GPX4 degradation and inhibiting the development of gastric cancer.
	•OTUD5, GPX4 expression and p53 activity are highly correlated and correlates with clinical progression in STAD.

Keywords

deubiquitinase / ferroptosis / GPX4 / OTUD5 / p53

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Junjing Zhang, Tongguan Tian, Xinxing Li, Kai Xu, Yao Lu, Xia Li, Xinyu Zhao, Ziyi Cui, Zhenxiang Wang, Yuefan Zhou, Yixin Xu, Hongchen Li, Yan Zhang, Yu Du, Lei Lv, Yanping Xu. p53 inhibits OTUD5 transcription to promote GPX4 degradation and induce ferroptosis in gastric cancer. Clinical and Translational Medicine, 2025, 15(3): e70271 DOI:10.1002/ctm2.70271

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.