%AYu, Fan [Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Columbus Ohio USA]%ALi, Yanhui [Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Columbus Ohio USA]%AYe, Qinmao [Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Columbus Ohio USA]%AMiao, Jiaxing [Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Columbus Ohio USA]%ATaleb, Sarah [Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Columbus Ohio USA]%AZhao, Yutong [Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Columbus Ohio USA]%AZhao, Jing [Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute The Ohio State University Columbus Ohio USA]%BJournal Name: Journal of Cellular Physiology; Journal Volume: 236; Journal Issue: 6; Related Information: CHORUS Timestamp: 2023-09-01 14:50:29 %D2020%IWiley Blackwell (John Wiley & Sons) %JJournal Name: Journal of Cellular Physiology; Journal Volume: 236; Journal Issue: 6; Related Information: CHORUS Timestamp: 2023-09-01 14:50:29 %K %MOSTI ID: 10257528 %PMedium: X %TLipopolysaccharide reduces USP13 stability through c‐Jun N‐terminal kinase activation in Kupffer cells %XAbstract

Protein ubiquitination regulates protein stability, cellular localization, and enzyme activity. Deubiquitinases catalyze the removal of ubiquitin from target proteins and reverse ubiquitination. USP13, a deubiquitinase, has been shown to regulate a variety of cellular responses including inflammation; however, the molecular regulation of USP13 has not been demonstrated. In this study, we revealed that USP13 is degraded in response to lipopolysaccharide (LPS) in Kupffer cells. USP13 levels are significantly decreased in inflamed organs, including liver tissues from septic mice. LPS reduces USP13 protein stability, not transcription, in Kupffer cells. Furthermore, LPS increases USP13 polyubiquitination. Inhibition of proteasome, but not lysosome or immunoproteasome, attenuates LPS‐induced USP13 degradation, suggesting USP13 degradation is mediated by the ubiquitin‐proteasome system. A catalytically inactive form of USP13 exhibits similar degree of degradation compared with USP13 wild‐type, suggesting that USP13 degradation is not dependent on its activity. Furthermore, USP13 degradation is dependent on new protein synthesis. Inhibition of c‐Jun N‐terminal kinase (JNK) attenuates USP13 degradation, indicating that JNK‐dependent new protein synthesis is necessary for USP13 degradation. This study reveals a molecular mechanism of regulation of USP13 degradation in Kupffer cells in response to bacterial endotoxin.

%0Journal Article