RNF138 inhibits late inflammatory gene transcription through degradation of SMARCC1 of the SWI/SNF complex
Wei Liu,
Ziqiao Wang,
Shuo Liu,
Xuan Zhang,
Xuetao Cao,
Minghong Jiang
Affiliations
Wei Liu
Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
Ziqiao Wang
Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China
Shuo Liu
Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China
Xuan Zhang
Department of Rheumatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China
Xuetao Cao
Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; Corresponding author
Minghong Jiang
Department of Immunology, Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; Corresponding author
Summary: As one of the core components of the switching or sucrose non-fermentable (SWI/SNF) complex, SMARCC1 (BAF155, SRG3) plays essential roles in activation of late inflammatory genes in response to microbial challenge. However, little is known about the mechanism of how SMARCC1 regulates the inflammatory innate response. Via functional screening, we identify the nuclear E3 ubiquitin ligase RNF138 as a negative regulator in the 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, the catalytic activity of RNF138 fine-tunes the kinetics of late inflammatory gene transcription by inhibiting chromatin remodeling at SWI/SNF-regulated gene loci. 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 the extent and duration of inflammatory responses.
