The deubiquitinase OTUD4 suppresses TAK1 kinase-dependent NF-κB signaling and inflammation.

ABSTRACT: Chronic inflammation contributes to the development of many cancers, including non-small cell lung cancer, and is characterized by persistent activation of proinflammatory NF-κB signaling. The mechanisms that restrain NF-κB signaling remain incompletely defined. Here, we identify the deubiquitinase ovarian tumor family deubiquitinase 4 (OTUD4) as a suppressor of tumor necrosis factor (TNF)-induced NF-κB activation and chronic inflammation. OTUD4 interacts with core components of the transforming growth factor β-activated kinase 1 (TAK1) signalosome, including TAK1, TAB1, and TAB3, and removes K63-linked polyubiquitin chains from substrates within this complex, such as TAK1 and TAB3, thereby reducing TNF-induced NF-κB signaling. A histidine-centered loop (His loop) in the catalytic domain i

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12607013 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature