Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation

• DOI: 10.7554/elife.87935.4
• Publication Date: 2024-09-13T13:50:57Z
• Authors: Jiansen Lu; Jiahuan Zhang; Huaji Jiang; Zhiqiang Hu; Yufen Zhang; Lian He; Jianwu Yang; Yingchao Xie; Dan Wu; Hongyu Li; Ke Zeng; Peng Tan; Qingyue Xiao; Zijing Song; Chenglong Pan; Xiaochun Bai; Xiao Yu
• Keywords: Proinflammatory cytokine

Van Gogh-like 2 (Vangl2), a core planar cell polarity component, plays an important role in polarized cellular and tissue morphology induction, growth development, cancer. However, its regulating inflammatory responses remains elusive. Here, we report that Vangl2 is upregulated patients with sepsis identify as negative regulator of The nuclear factor-kappaB (NF-κB) signaling by the protein stability activation transcription component p65. Mice myeloid-specific deletion ( ΔM ) are hypersusceptible to lipopolysaccharide (LPS)-induced septic shock. Vangl2-deficient myeloid cells exhibit enhanced phosphorylation expression p65, therefore, promoting secretion proinflammatory cytokines after LPS stimulation. Mechanistically, NF-κB signaling-induced-Vangl2 recruits E3 ubiquitin ligase PDLIM2 catalyze K63-linked ubiquitination on which serves recognition signal for cargo receptor NDP52-mediated selective autophagic degradation. Taken together, these findings demonstrate suppressor NF-κB-mediated inflammation provide insights into crosstalk between autophagy diseases.