USP14-mediated NLRC5 upregulation inhibits endothelial cell activation and inflammation in atherosclerosis

Fu, Yuan; Qiu, Junxiong; Wu, Jianhua; Zhang, Lisui; Wei, Feng; Lu, Liuyi; Wang, Chao; Zeng, Zhaopei; Liang, Shi; Zheng, Junmeng

doi:10.1016/j.bbalip.2022.159258

Cited by 5 publications

(10 citation statements)

References 70 publications

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“…Studies indicate that USP9X, USP10, USP14, USP17, USP20, and USP36 play regulatory roles in the atherosclerotic process ( Table 3 ). Macrophages intake an excess of lipids, leading to the proliferation of macrophages and secrete inflammatory factors, which causes the formation of foam cells, thus aggravating atherosclerosis ( 49 , 52 , 54 ). This process hinges on receptor activity, including CD36, SR-A, and SR-B1 ( 57 ).…”

Section: Roles Of Usps In Inflammatory Diseasesmentioning

confidence: 99%

Roles of ubiquitin-specific proteases in inflammatory diseases

Chen,

Zhang,

et al. 2024

Front. Immunol.

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Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate the fate of proteins and signaling pathway transduction by removing ubiquitin chains from the target proteins. USPs are essential for the modulation of a variety of physiological processes, such as DNA repair, cell metabolism and differentiation, epigenetic modulations as well as protein stability. Recently, extensive research has demonstrated that USPs exert a significant impact on innate and adaptive immune reactions, metabolic syndromes, inflammatory disorders, and infection via post-translational modification processes. This review summarizes the important roles of the USPs in the onset and progression of inflammatory diseases, including periodontitis, pneumonia, atherosclerosis, inflammatory bowel disease, sepsis, hepatitis, diabetes, and obesity. Moreover, we highlight a comprehensive overview of the pathogenesis of USPs in these inflammatory diseases as well as post-translational modifications in the inflammatory responses and pave the way for future prospect of targeted therapies in these inflammatory diseases.

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Section: Roles Of Usps In Inflammatory Diseasesmentioning

confidence: 99%

Roles of ubiquitin-specific proteases in inflammatory diseases

Chen,

Zhang,

et al. 2024

Front. Immunol.

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“…Given that smooth muscle cells exert this phenotypic switch in atherosclerotic lesions [ 220 ], USP14 in smooth muscle cells appears to trigger atherosclerosis. In contrast to the function of USP14 in smooth muscle, Fu et al reported that the expression of Usp14 was significantly downregulated in oxidized LDL-stimulated endothelial cells [ 221 ]. Moreover, overexpression of Usp14 in endothelial cells interfered with NF-κB activation by deubiquitinating the NOD-like receptor family cascade recruitment domain family domain containing 5 (NLRC5) [ 221 ], which inhibits NF-κB activation [ 222 ].…”

Section: Atherosclerosismentioning

confidence: 99%

“…In contrast to the function of USP14 in smooth muscle, Fu et al reported that the expression of Usp14 was significantly downregulated in oxidized LDL-stimulated endothelial cells [ 221 ]. Moreover, overexpression of Usp14 in endothelial cells interfered with NF-κB activation by deubiquitinating the NOD-like receptor family cascade recruitment domain family domain containing 5 (NLRC5) [ 221 ], which inhibits NF-κB activation [ 222 ]. Furthermore, infection with Usp14 -expressing adenovirus halted the progression of atherosclerosis in apolipoprotein E ( Apoe ) KO mice [ 221 ].…”

Section: Atherosclerosismentioning

confidence: 99%

“…Moreover, overexpression of Usp14 in endothelial cells interfered with NF-κB activation by deubiquitinating the NOD-like receptor family cascade recruitment domain family domain containing 5 (NLRC5) [ 221 ], which inhibits NF-κB activation [ 222 ]. Furthermore, infection with Usp14 -expressing adenovirus halted the progression of atherosclerosis in apolipoprotein E ( Apoe ) KO mice [ 221 ]. Therefore, endothelial USP14 plays a suppressive role in inflammation of atherosclerotic lesions.…”

Section: Atherosclerosismentioning

confidence: 99%

“…Full-length USP14, or the UBL domain of USP14, blocks target digestion by the proteasome via an allosteric mechanism [ 245 ], whereas the ligation of an ubiquitylated target to USP14 potentiates proteasomal ATPase activity and 20S core particle opening, followed by proteasomal digestion [ 245 ]. With respect to the modulation of key molecules for metabolic diseases, such as FASN and CBP [ 103 , 221 ], USP14 might not only disassemble the ubiquitin chain on target proteins, but might also affect the incorporation of the targets into the proteasome. Interestingly, USP14 binds PSMD7, a regulatory subunit of the 19S proteasome [ 217 ].…”

Section: Perspectivesmentioning

confidence: 99%

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Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders

Kitamura

2023

IJMS

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Ubiquitination and deubiquitination are reversible processes that modify the characteristics of target proteins, including stability, intracellular localization, and enzymatic activity. Ubiquitin-specific proteases (USPs) constitute the largest deubiquitinating enzyme family. To date, accumulating evidence indicates that several USPs positively and negatively affect metabolic diseases. USP22 in pancreatic β-cells, USP2 in adipose tissue macrophages, USP9X, 20, and 33 in myocytes, USP4, 7, 10, and 18 in hepatocytes, and USP2 in hypothalamus improve hyperglycemia, whereas USP19 in adipocytes, USP21 in myocytes, and USP2, 14, and 20 in hepatocytes promote hyperglycemia. In contrast, USP1, 5, 9X, 14, 15, 22, 36, and 48 modulate the progression of diabetic nephropathy, neuropathy, and/or retinopathy. USP4, 10, and 18 in hepatocytes ameliorates non-alcoholic fatty liver disease (NAFLD), while hepatic USP2, 11, 14, 19, and 20 exacerbate it. The roles of USP7 and 22 in hepatic disorders are controversial. USP9X, 14, 17, and 20 in vascular cells are postulated to be determinants of atherosclerosis. Moreover, mutations in the Usp8 and Usp48 loci in pituitary tumors cause Cushing syndrome. This review summarizes the current knowledge about the modulatory roles of USPs in energy metabolic disorders.

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