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Advanced Science

Advanced Science

IF: 14.3
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UFMylation of NLRP3 Prevents Its Autophagic Degradation and Facilitates Inflammasome Activation

Published:22 February 2025 DOI: 10.1002/advs.202406786 PMID: 39985286
Jiongjie Jing, Fan Yang, Ke Wang, Mintian Cui, Ni Kong, Shixi Wang, Xiaoyue Qiao, Fanyu Kong, Dongyang Zhao, Jinlu Ji, Lunxian Tang, Jiaxin Gao, Yu-Sheng Cong, Deqiang Ding, Kun Chen

Abstract

NLRP3 (NOD, LRR and pyrin domain-containing protein 3) inflammasome is important for host defense against infections and maintaining homeostasis. Aberrant activation of NLRP3 inflammasome is closely related to various inflammatory diseases. Post-translational modifications are critical for NLRP3 inflammasome regulation. However, the mechanism of NLRP3 inflammasome activation remains incompletely understood. Here, it is demonstrated that the Ufm1 E3 ligase Ufl1 mediated UFMylation is essential for NLRP3 inflammasome activation. Mechanistically, Ufl1 binds and UFMylates NLRP3 in the priming stage of NLRP3 activation, thereby sustaining the stability of NLRP3 by preventing NLRP3 K63-linked ubiquitination and the subsequent autophagic degradation. It is further demonstrated that myeloid cell-specific Ufl1 or Ufm1 deficiency in mice significantly alleviated inflammatory responses and tissue damage following lipopolysaccharide (LPS)-induced endotoxemia and alum-induced peritonitis. Thus, the findings offer new insights into potential therapeutic targets for NLRP3 inflammasome-related diseases by targeting the UFMylation system.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
MG-132 133407-82-6 C26H41N3O5 426 suppliers $11.00-$3568.00
MG-132 133407-82-6 C26H41N3O5 426 suppliers $11.00-$3568.00
MG-132 133407-82-6 C26H41N3O5 426 suppliers $11.00-$3568.00
MG-132 133407-82-6 C26H41N3O5 426 suppliers $11.00-$3568.00
Thapsigargin 67526-95-8 C34H50O12 212 suppliers $37.00-$3800.00
Thapsigargin 67526-95-8 C34H50O12 212 suppliers $37.00-$3800.00
Thapsigargin 67526-95-8 C34H50O12 212 suppliers $37.00-$3800.00
Thapsigargin 67526-95-8 C34H50O12 212 suppliers $37.00-$3800.00

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