USP8 inhibition regulates autophagy flux and controls Salmonella infection.
USP8 inhibition regulates autophagy flux and controls Salmonella infection.
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USP8抑制调节自噬通量并控制沙门氏菌感染。
DOI：
10.3389/fcimb.2023.1070271
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发表时间：
2023
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
--
作者：
泛素化是一种重要的蛋白质修饰，调节各种必需的细胞过程，包括先天免疫细胞的功能。去泛素化酶是负责从底物中去除泛素修饰的酶，并且在鼠伤寒沙门氏菌和小肠结肠炎耶尔森氏菌感染期间巨噬细胞中去泛素化酶的调节仍然未知。为了鉴定在细菌感染期间在人巨噬细胞中调节的去泛素化酶，进行了基于活性的蛋白质组学筛选。研究了所鉴定的去泛素化酶USP 8的药理学抑制作用，包括其对巨噬细胞内细菌存活的影响及其在沙门氏菌感染期间自噬调节中的作用。在感染的巨噬细胞中，几种去泛素化酶受到不同的调节。其中一种去泛素化酶是USP8，它在沙门氏菌感染后下调。USP8的抑制与巨噬细胞内细菌存活的减少有关，并且发现它在沙门氏菌感染期间调节自噬中发挥独特的作用。USP8的抑制导致p62自噬衔接子的下调。这项研究的结果表明，USP8在调节自噬通量方面具有新的作用，这限制了细胞内细菌，特别是在沙门氏菌感染期间。
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. 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. 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. 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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影响因子：
3.4
作者：
Colombo, Matteo;Vallese, Stefania;Guedat, Philippe
通讯作者：
Guedat, Philippe
影响因子：
6.2
作者：
Edelmann MJ;Nicholson B;Kessler BM
通讯作者：
Kessler BM
影响因子：
6.7
作者：
Coward C;Restif O;Dybowski R;Grant AJ;Maskell DJ;Mastroeni P
通讯作者：
Mastroeni P
影响因子：
4.1
作者：
Edelmann, Mariola J.;Iphofer, Alexander;Kessler, Benedikt M.
通讯作者：
Kessler, Benedikt M.
影响因子：
4.5
作者：
MacDonald, Ewan;Urbe, Sylvie;Clague, Michael J.
通讯作者：
Clague, Michael J.