Proteomics

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DDX3X SUMOylation Promotes Septic Inflammation by Enhancing NLRP3 Inflammasome Activation


ABSTRACT: This study investigates the role of DDX3X SUMOylation in the activation of the NLRP3 inflammasome during sepsis. We demonstrate that SUMOylation of DDX3X, regulated by the SUMO protease SENP1, is a crucial trigger for NLRP3 inflammasome activation. In endotoxemia and sepsis models, the absence of SENP1 in macrophages and mice led to increased NLRP3 inflammasome activation. Mechanistically, DDX3X SUMOylation promoted the interaction of NLRP3 at lysine 118, inhibiting K48-conjugated ubiquitination and subsequent degradation of NLRP3 by the deubiquitinase OTUD6A, resulting in enhanced oligomerization of NLRP3. In murine adoptive transfer experiments, macrophages expressing the SUMOylation-inhibiting mutation DDX3X-K118R suppressed NLRP3 inflammasome activation, providing protection against LPS-induced inflammatory lung injury. These findings suggest that SENP1-mediated DDX3X deSUMOylation regulates NLRP3 inflammasome activation, offering a potential therapeutic avenue to mitigate NLRP3-induced inflammation.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Macrophage

DISEASE(S): Bacterial Sepsis

SUBMITTER: xuedi zhang  

LAB HEAD: xuedi zhang

PROVIDER: PXD060598 | Pride | 2025-03-06

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
YAS202212080041_1_IGG.raw Raw
YAS202212080041_1_IP.raw Raw
uniprot_Homo_sapiens_203800_20220104.zip Other
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