The PGAM5–NEK7 interaction is a therapeutic target for NLRP3 inflammasome activation in colitis

• DOI: 10.1016/j.apsb.2024.11.019
• Publication Date: 2024-11-27T00:11:30Z
• Authors: Cheng-Long Gao; Jinqian Song; Haojie Wang; Qinghong Shang; Xin Guan; Gang Xu; Jiayang Wu; Dalei Wu; Yueqin Zheng; Xudong Wu; Feng Zhao; Xindong Liu; Lei Shi; Tao Pang
• Keywords: Protein–protein interaction; Punicalagin; APEX2 proximity labeling; NEK7; Therapeutics. Pharmacology; RM1-950; NLRP3 inflammasome; PGAM5

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 a mitochondrial phosphatase activation macrophages. However, role colitis and mechanisms underlying regulating activity remain unknown. Here, we show that deficiency ameliorates dextran sodium sulfate (DSS)-induced mice via suppressing activation. By combining APEX2-based proximity labeling focused on with quantitative proteomics, identify NEK7 as new binding partner to promote assembly activity-independent manner upon induction. Interfering PGAM5-NEK7 interaction by punicalagin inhibits macrophages DSS-induced mice. Altogether, our data demonstrate for further provide promising therapeutic strategy blocking interaction.