Disrupting the TRAF1/cIAP2 interaction attenuates inflammasome activation and protects against monosodium urate crystal-induced arthritis.

ABSTRACT: Tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) regulates NF-κB signaling and is implicated in chronic autoimmune diseases characterized by persistent inflammation. In addition to its role in restraining linear ubiquitin assembly complex-mediated linear ubiquitination of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) to limit inflammasome activation, TRAF1 also stabilizes cellular inhibitor of apoptosis protein 2 (cIAP2) by protecting it from degradation. Notably, cIAP2 promotes inflammasome activation via K63-linked polyubiquitination of caspase-1. Here, we show that disrupting the TRAF1/cIAP2 interaction (V203A in humans; V196A in mice) reduces inflammasome activation. TRAF1V203A THP-1 cells exhibit diminished caspase-1 ubiquitinat

SUBMITTER: Madahar SS 

PROVIDER: S-EPMC12643475 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature