TRAF3 promotes ROS production and pyroptosis by targeting ULK1 ubiquitination in macrophages

• DOI: 10.1096/fj.201903073r
• Publication Date: 2020-04-10T11:45:06Z
• Authors: Yang Shen; Wen‐wen Liu; Xiu Zhang; Jian‐guo Shi; Shan Jiang; Lishuang Zheng; Yan Qin; Bin Liu; Jian‐hong Shi
• Keywords: ULK1; Pyroptosis

Disrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage oxidative stress-induced macrophage inflammatory cell death. It remains unclear how dysfunction relates to inflammasome activation pyroptotic In this study, we demonstrated that tumor necrosis factor receptor-associated 3 (TRAF3) regulates ROS production promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced pyroptosis in mouse primary macrophages human monocyte THP-1 cells. Co-IP assays confirmed TRAF3 forms a complex with TRAF2 cIAP1 mediates ubiquitin degradation of Unc-51 like autophagy activating kinase 1 (ULK1). Moreover, knockdown ULK1 cells significantly promoted LPS/Ng-induced by caspase mature IL-1β. Apoptosis inducing (AIF) translocation from nuclear was observed ULK1-deficient under LPS/Ng stimulation, which death deficient macrophages. conclusion, study identified novel role regulation ubiquitination signaling provided molecular mechanisms controls production, activity, AIF-dependent pyroptosis.