Mouse RNF138 immunoprecipitation mass spectrography analysis in macrophages

As one of the core components of the SWI/SNF complex, SMARCC1 (BAF155, SRG3) plays essential roles in activation of the late inflammatory genes in response to microbial challenge. However, little is known about the mechanism how SMARCC1 regulates the inflammatory innate response. Via functional screening, we identify nuclear E3 ubiquitin ligase RNF138 as a negative regulator in inflammatory innate response, and show that RNF138 interacts with SMARCC1 and mediates its K48-linked polyubiquitination at position Lys643 and proteasomal degradation. As a result, catalytic activity of RNF138 fine-tunes the kinetics of late inflammatory gene transcription by inhibiting chromatin remodeling at SWI/SNF regulated gene loci. The reduced RNF138 and increased SMARCC1 in monocytes of rheumatoid arthritis patients are observed. These results provide mechanistic insight into the interplay among nucleosome remodeling, inflammation and ubiquitylation, and underscore the important role of the E3 ubiquitin ligases in controlling both extent and duration of inflammatory responses.