Recently, professor Gao Chengjiang and his team published a paper in Autophagy (Cas 1 Area,IF:16.02) published a study entitled” USP5 attenuates NLRP3 inflammasome Activation by promoting autophagic degradation of NLRP3” online.CAI Baoshan and Zhao Jian, PhD students from The School of Basic Medical Sciences of Shandong University, are the co-first authors of this paper. Professor Gao Chengjiang and Assistant researcher Liu Bingyu from the School of Basic Medical Sciences of Shandong University are the co-corresponding authors of this paper. Shandong University is the first and only corresponding author.

USP5 is a member of the USP deubiquitination enzyme family. In this study, software prediction and protein co-localization analysis showed that USP5 was localized to lysosome/autophagosome, further confirming that USP5 plays a key regulatory role in NLRP3 inflammasome activation. Overexpression of USP5 inhibits LPS-induced and ATP-induced IL-1β production. The peritonitis induced by alum was relieved. Further mechanistic studies have shown that USP5, as a scaffold protein, can recruit E3 ubiquitin ligase MARCH7, selectively promote the polyubiquitin modification of NLRP3 K48 link, and mediate NLRP3 into the autophagy degradation pathway, promoting NLRP3 protein degradation, thereby inhibiting the activation of inflammasome. This study provides new insights into the regulatory mechanisms of NLRP3 inflammasome overactivation and inflammatory natural immune responses, and provides new potential therapeutic targets for the treatment and prevention of related diseases.

Paper link: https://doi.org/10.1080/15548627.2021.1965426