USP50-mediated NLRP3 deubiquitination enhances NLRP3 inflammasome activation to suppress HCC metastasis.

ABSTRACT: The nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is downregulated in hepatocellular carcinoma (HCC), and its stability is regulated by ubiquitination. However, the regulatory mechanisms underlying NLRP3 deubiquitination and its role in HCC metastasis remains unclear. We demonstrated that ubiquitin-specific protease 50 (USP50) directly interacts with NLRP3, exhibiting deubiquitinase (DUB) activity through specific cleavage of K48-linked polyubiquitination chains to stabilize NLRP3 by preventing proteasomal degradation. Clinically, we observed that low NLRP3 and high β-catenin levels were negatively correlated in HCC specimens. Subsequent mechanistic exploration confirmed that NLRP3 exerts negative regulation on β-catenin by binding with glycog

SUBMITTER: Gong Z 

PROVIDER: S-EPMC12703871 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature