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

Lu, Jiansen1,2; Zhang, Jiahuan3; Jiang, Huaji2,4; Hu, Zhiqiang2; Zhang, Yufen2; He, Lian5,6; Yang, Jianwu2; Xie, Yingchao2; Wu, Dan2; Li, Hongyu2; Zeng, Ke2; Tan, Peng5,7; Xiao, Qingyue8; Song, Zijing8; Pan, Chenglong1; Bai, Xiaochun8; Yu, Xiao2,3,9

2024-09-13

10.7554/eLife.87935.4.sa4

ELIFE   影响因子和分区

2050-084X

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

Vangl2 NF-kappa B signaling selective autophagy PDLIM2 ubiquitin Human Mouse

SCI

英语

其他

National Natural Science Foundation of China[NDP52] ; National Natural Science Foundation of China["82171741","82371761","82302731"] ; Guangdong Basic and Applied Basic Research Foundation[2021A1515012140] ; China Postdoctoral Science Foundation[2021M701622]

Life Sciences & Biomedicine - Other Topics

Biology

WOS:001312360600001

eLIFE SCIENCES PUBL LTD

Web of Science

1.Southern Med Univ, Affiliated Hosp 5, Dept Joint Surg, Guangzhou, Peoples R China
2.Southern Med Univ, Sch Basic Med Sci, Dept Immunol, Guangzhou, Peoples R China
3.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Clin Lab Med, Guangzhou, Peoples R China
4.Shantou Univ, Yuebei Peoples Hosp, Med Coll, Dept Orthopaed, Shaoguan, Peoples R China
5.Southern Univ Sci & Technol, Sch Med, Dept Pharmacol, Shenzhen, Peoples R China
6.Texas A&M Univ, Inst Biosci & Technol, Coll Med, Houston, TX USA
7.Broad Inst MIT & Harvard, Klarman Cell Observ, Cambridge, MA USA
8.Southern Med Univ, Sch Basic Med Sci, Dept Cell Biol, Guangzhou, Peoples R China
9.Southern Med Univ, Guangdong Prov Key Lab Single Cell Technol & Appli, Guangzhou, Peoples R China

Lu, Jiansen,Zhang, Jiahuan,Jiang, Huaji,et al. Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation[J]. ELIFE,2024,12.

Lu, Jiansen.,Zhang, Jiahuan.,Jiang, Huaji.,Hu, Zhiqiang.,Zhang, Yufen.,...&Yu, Xiao.(2024).Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation.ELIFE,12.

Lu, Jiansen,et al."Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation".ELIFE 12(2024).