| Literature DB >> 35217790 |
Yunhua Peng1, Jing Liu2, Zhen Wang1, Chunping Cui3, Tiantian Zhang1, Shuangxi Zhang1, Peipei Gao1, Zhanwu Hou1, Huadong Liu1, Jianping Guo4, Jinfang Zhang5, Yurong Wen6, Wenyi Wei2, Lingqiang Zhang7, Jiankang Liu8,9, Jiangang Long10.
Abstract
MYC drives the tumorigenesis of human cancers, including prostate cancer (PrCa), thus deubiquitinase (DUB) that maintains high level of c-Myc oncoprotein is a rational therapeutic target. Several ubiquitin-specific protease (USP) family members of DUB have been reported to deubiquitinate c-Myc, but none of them is the physiological DUB for c-Myc in PrCa. By screening all the DUBs, here we reveal that OTUD6A is exclusively amplified and overexpressed in PrCa but not in other cancers, eliciting a prostatic-specific oncogenic role through deubiquitinating and stabilizing c-Myc oncoprotein. Moreover, genetic ablation of OTUD6A efficiently represses prostatic tumorigenesis of both human PrCa cells and the Hi-Myc transgenic PrCa mice, via reversing the metabolic remodeling caused by c-Myc overexpression in PrCa. These results indicate that OTUD6A is a physiological DUB for c-Myc in PrCa setting and specifically promotes prostatic tumorigenesis through stabilizing c-Myc oncoprotein, suggesting that OTUD6A could be a unique therapeutic target for Myc-driven PrCa.Entities:
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Year: 2022 PMID： 35217790 PMCID： PMC9433443 DOI： 10.1038/s41418-022-00960-x
Source DB: PubMed Journal: Cell Death Differ ISSN： 1350-9047 Impact factor: 12.067