ASB17 Facilitates the Burst of LPS-Induced Inflammation Through Maintaining TRAF6 Stability.

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.

• Authors: Pin Wan, Ge Yang, Simeng Zhang, Yaru Zhang, Yaling Jia, Xu Che, Zhen Luo, Pan Pan, Geng Li, Xulin Chen, Qiwei Zhang, Wen Zhang, Qiuping Tan, Yongkui Li, Jianguo Wu
• Journal: Frontiers in cellular and infection microbiology (Front Cell Infect Microbiol) Vol. 12 Pg. 759077 ( 2022) ISSN: 2235-2988 [Electronic] Switzerland
• PMID: 35174103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Wan, Yang, Zhang, Zhang, Jia, Che, Luo, Pan, Li, Chen, Zhang, Zhang, Tan, Li and Wu.

Chemical References

• Intracellular Signaling Peptides and Proteins
• Lipopolysaccharides
• NF-kappa B
• Tifab protein, human
• TNF Receptor-Associated Factor 6
• ASB17 protein, human

Topics

• Animals
• Humans
• Mice
• Inflammation (metabolism)
• Intracellular Signaling Peptides and Proteins (genetics)
• Lipopolysaccharides (metabolism)
• NF-kappa B (metabolism)
• TNF Receptor-Associated Factor 6 (metabolism)
• Ubiquitination