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USP8 inhibition regulates autophagy flux and controls Salmonella infection
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SYSNO ASEP 0571023 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title USP8 inhibition regulates autophagy flux and controls Salmonella infection Author(s) Santelices, J. (US)
Ou, M. (US)
Maegawa, G. H. B. (US)
Hercík, Kamil (UOCHB-X)
Edelmann, M. J. (US)Article number 1070271 Source Title Frontiers in Cellular and Infection Microbiology. - : Frontiers Media - ISSN 2235-2988
Roč. 13, March (2023)Number of pages 12 s. Language eng - English Country CH - Switzerland Keywords deubiquitinating enzymes ; deubiquitinases ; Salmonella ; USP8 ; autophagy ; chemical proteomics OECD category Medicinal chemistry Method of publishing Open access Institutional support UOCHB-X - RVO:61388963 UT WOS 000962124300001 EID SCOPUS 85151509577 DOI 10.3389/fcimb.2023.1070271 Annotation Introduction: Ubiquitination is an important protein modification that regulates various essential cellular processes, including the functions of innate immune cells. Deubiquitinases are enzymes responsible for removing ubiquitin modification from substrates, and the regulation of deubiquitinases in macrophages during infection with Salmonella Typhimurium and Yersinia enterocolitica remains unknown. Methods: To identify deubiquitinases regulated in human macrophages during bacterial infection, an activity-based proteomics screen was conducted. The effects of pharmacological inhibition of the identified deubiquitinase, USP8, were examined, including its impact on bacterial survival within macrophages and its role in autophagy regulation during Salmonella infection. Results: Several deubiquiitnases were differentially regulated in infected macrophages. One of the deubiquitinases identified was USP8, which was downregulated upon Salmonella infection. Inhibition of USP8 was associated with a decrease in bacterial survival within macrophages, and it was found to play a distinct role in regulating autophagy during Salmonella infection. The inhibition of USP8 led to the downregulation of the p62 autophagy adaptor. Discussion: The findings of this study suggest a novel role of USP8 in regulating autophagy flux, which restricts intracellular bacteria, particularly during Salmonella infection. Workplace Institute of Organic Chemistry and Biochemistry Contact asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Year of Publishing 2024 Electronic address https://doi.org/10.3389/fcimb.2023.1070271
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