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USP8 inhibition regulates autophagy flux and controls Salmonella infection
J. Santelices, M. Ou, GHB. Maegawa, K. Hercik, MJ. Edelmann
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.
Grantová podpora
R61 NS118407
NINDS NIH HHS - United States
R21 NS106406
NINDS NIH HHS - United States
Free Medical Journals od 2011
PubMed Central od 2011
Europe PubMed Central od 2011
Open Access Digital Library od 2011-01-01
Open Access Digital Library od 2011-01-01
ROAD: Directory of Open Access Scholarly Resources od 2011
Odkazy
PubMed
37026055
DOI
10.3389/fcimb.2023.1070271
Knihovny.cz E-zdroje
- MeSH
- autofagie MeSH
- deubikvitinasy metabolismus MeSH
- endopeptidasy genetika MeSH
- endozomální třídící komplexy pro transport genetika MeSH
- lidé MeSH
- Salmonella typhimurium metabolismus MeSH
- salmonelóza * MeSH
- thiolesterasa ubikvitinu genetika metabolismus MeSH
- ubikvitinace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
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.
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- $a 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.
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