The ubiquitin-specific protease 21 is critical for cancer cell mitochondrial function and regulates proliferation and migration.

Autor:	Kulma M; Molecure SA, Warsaw, Poland. Electronic address: m.kulma@molecure.com., Hofman B; Molecure SA, Warsaw, Poland., Szostakowska-Rodzoś M; Molecure SA, Warsaw, Poland., Dymkowska D; Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland., Serwa RA; IMol, Polish Academy of Sciences, Warsaw, Poland; ReMedy International Research Agenda Unit, IMol, Polish Academy of Sciences, Warsaw, Poland., Piwowar K; Molecure SA, Warsaw, Poland., Belczyk-Ciesielska A; Molecure SA, Warsaw, Poland., Grochowska J; Molecure SA, Warsaw, Poland., Tuszyńska I; Molecure SA, Warsaw, Poland., Muchowicz A; Molecure SA, Warsaw, Poland., Drzewicka K; Molecure SA, Warsaw, Poland., Zabłocki K; Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland., Zasłona Z; Molecure SA, Warsaw, Poland.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Oct; Vol. 300 (10), pp. 107793. Date of Electronic Publication: 2024 Sep 19.
DOI:	10.1016/j.jbc.2024.107793
Abstrakt:	Ubiquitin-specific proteases (USPs) are the main members of deubiquitinases (DUBs) that catalyze removing ubiquitin chains from target proteins, thereby modulating their half-life and function. Enzymatic activity of USP21 regulates protein degradation which is critical for maintaining cell homeostasis. USP21 determines the stability of oncogenic proteins and therefore is implicated in carcinogenesis. In this study, we investigated the effect of USP21 deletion on cancer cell metabolism. Transcriptomic and proteomic analysis of USP21 KO HAP-1 cells revealed that endogenous USP21 is critical for the expression of genes and proteins involved in mitochondrial function. Additionally, we have found that the deletion of USP21 reduced STAT3 activation and STAT3-dependent gene and protein expression in cancer cells. Genetic deletion of USP21 impaired mitochondrial respiration and disturbed ATP production. This resulted in cellular consequences such as inhibition of cell proliferation and migration. Presented results provide new insights into the biology of USP21, suggesting novel mechanisms for controlling STAT3 activity and mitochondrial function in tumor cells. Taken together, our findings indicate that targeting USP21 dysregulates the energy status of cancer cells offering new perspectives for anticancer therapy. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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