SENP6 Restrains NLRP3 Inflammasome Activation via DeSUMOylation-Driven K48-Linked Ubiquitination of NLRP3 in Acute Lung Injury.

ABSTRACT: The NLRP3 inflammasome is a pivotal component of the innate immune system, responding to infections and cellular damage. Its dysregulation has been implicated in numerous inflammatory diseases, although the mechanisms controlling its activation remain incompletely elucidated. Recent studies have highlighted the importance of posttranslational modifications, such as ubiquitination and SUMOylation, in regulating inflammasome activation. In this study, we demonstrate that SENP6, a SUMO-specific protease, negatively regulates NLRP3 inflammasome activation by promoting K48-linked polyubiquitination of NLRP3. SENP6-deficient macrophages exhibit enhanced NLRP3 activation and increased secretion of interleukin-1β (IL-1β) and IL-18, resulting in amplified inflammatory responses. Mechanistically, SE

SUBMITTER: Gu A 

PROVIDER: S-EPMC12794193 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature