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• W2107181461 abstract "Abstract Cancer cells are characterized by altered ubiquitination of many proteins. The ubiquitin-specific protease 2a (USP2a) is a deubiquitinating enzyme overexpressed in prostate adenocarcinomas, where it exhibits oncogenic behavior in a variety of ways including targeting c-Myc via the miR-34b/c cluster. Here we demonstrate that USP2a induces drug resistance in both immortalized and transformed prostate cells. Specifically, it confers resistance to typically pro-oxidant agents, such as cisplatin (CDDP) and doxorubicin (Doxo), and to taxanes. USP2a overexpression protects from drug-induced oxidative stress by reducing reactive oxygen species (ROS) production and stabilizing the mitochondrial membrane potential (ΔΨ), thus impairing downstream p38 activation and triggering of apoptosis. The molecular mediator of the USP2a protective function is the glutathione (GSH). Through miR-34b/c-driven c-Myc regulation, USP2a increases intracellular GSH content, thus interfering with the oxidative cascade triggered by chemotherapeutic agents. In light of these findings, targeting Myc and/or miR-34b/c might revert chemo-resistance." @default.
• W2107181461 created "2016-06-24" @default.
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• W2107181461 date "2013-09-26" @default.
• W2107181461 modified "2023-10-17" @default.
• W2107181461 title "USP2a alters chemotherapeutic response by modulating redox" @default.
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• W2107181461 doi "https://doi.org/10.1038/cddis.2013.289" @default.
• W2107181461 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3789164" @default.
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