Author:
Wan Pin,Yang Ge,Zhang Simeng,Zhang Yaru,Jia Yaling,Che Xu,Luo Zhen,Pan Pan,Li Geng,Chen Xulin,Zhang Qiwei,Zhang Wen,Tan Qiuping,Li Yongkui,Wu Jianguo
Abstract
ASB17, a member of the ankyrin repeat and SOCS box-containing protein (ASB) family, has been supposed to act as an E3 ubiquitin ligase. Actually, little is known about its biological function. In this study, we found that ASB17 knocking-out impaired the expression of the pro-inflammatory cytokines CCL2 and IL-6 in bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS), indicating an inflammation-promoting role of this gene. We reveal that ASB17 promotes LPS-induced nuclear factor kappa B (NF-κB) signal activation through interacting with TNF receptor-associated factor 6 (TRAF6) which is a crucial adaptor protein downstream of toll-like receptors (TLR). ASB17 via its aa177–250 segment interacts with the Zn finger domain of TRAF6. The interaction of ASB17 stabilizes TRAF6 protein through inhibiting K48-linked TRAF6 polyubiquitination. Therefore, we suggest that ASB17 facilitates LPS-induced NF-κB activation by maintaining TRAF6 protein stability. The inflammation enhancer role of ASB17 is recognized here, which provides new understanding of the activation process of inflammation and immune response.
Funder
National Natural Science Foundation of China-China Academy of General Technology Joint Fund for Basic Research
Subject
Infectious Diseases,Microbiology (medical),Immunology,Microbiology
Cited by
2 articles.
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