Cereblon suppresses the lipopolysaccharide-induced inflammatory response by promoting the ubiquitination and degradation of c-Jun

The Journal of Biological Chemistry
Jing YangGuoqiang Xu

Abstract

Chronic inflammation is associated with multiple human disorders, such as rheumatoid arthritis, metabolic diseases, and neurodegenerative diseases. Therefore, alleviation of inflammation induced by environmental stimuli is important for disease prevention or treatment. Cereblon (CRBN) functions as a substrate receptor of the cullin-4 RING E3 ligase to mediate protein ubiquitination and degradation. Although it has been reported that CRBN reduces the inflammatory response through its nonenzymatic function, its role as a substrate receptor of the E3 ligase is not explored in mediating this process. Here we used a quantitative proteomics approach to find that the major component of the activator protein 1 (AP-1) complex, c-Jun, is significantly down-regulated upon CRBN expression. Biochemical approaches further discover that CRBN interacts and partially colocalizes with c-Jun and promotes the formation of Lys48-linked polyubiquitin chains on c-Jun, enhancing c-Jun degradation. We further reveal that CRBN attenuates the transcriptional activity of the AP-1 complex and reduces the mRNA expression and protein level of several pro-inflammatory cytokines. Moreover, flow cytometry analyses show that CRBN attenuates lipopolysaccharide-in...Continue Reading

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Jan 28, 2020·Biochemical and Biophysical Research Communications·Tomotaka KuriharaNaoya Sawamura
Sep 24, 2021·Pflügers Archiv : European journal of physiology·Hyoung Kyu KimJin Han

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