气候变化领域集成服务门户(CCPortal): An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis

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DOI	10.1073/pnas.2015416118
	An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis
	Hou P.; Jia P.; Yang K.; Li Z.; Tian T.; Lin Y.; Zeng W.; Xing F.; Chen Y.; Li C.; Liu Y.; Guo D.
发表日期	2021
ISSN	00278424
卷号	118 期号:3
英文摘要	Nuclear factor κB (NF-κB)–mediated signaling pathway plays a crucial role in the regulation of inflammatory process, innate and adaptive immune responses. The hyperactivation of inflammatory response causes host cell death, tissue damage, and autoinflammatory disorders, such as sepsis and inflammatory bowel disease. However, how these processes are precisely controlled is still poorly understood. In this study, we demonstrated that ankyrin repeat and suppressor of cytokine signaling box containing 1 (ASB1) is involved in the positive regulation of inflammatory responses by enhancing the stability of TAB2 and its downstream signaling pathways, including NF-κB and mitogen-activated protein kinase pathways. Mechanistically, unlike other members of the ASB family that induce ubiquitination-mediated degradation of their target proteins, ASB1 associates with TAB2 to inhibit K48-linked polyubiquitination and thereby promote the stability of TAB2 upon stimulation of cytokines and lipopolysaccharide (LPS), which indicates that ASB1 plays a noncanonical role to further stabilize the target protein rather than induce its degradation. The deficiency of Asb1 protects mice from Salmonella typhimurium– or LPS-induced septic shock and increases the survival of mice. Moreover, Asb1-deficient mice exhibited less severe colitis and intestinal inflammation induced by dextran sodium sulfate. Given the crucial role of ASB proteins in inflammatory signaling pathways, our study offers insights into the immune regulation in pathogen infection and inflammatory disorders with therapeutic implications. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ASB1 \| inflammatory response \| NF-κB \| TAB2 \| ubiquitination
语种	英语
scopus关键词	ankyrin; ankyrin repeat and suppressor of cytokine signaling box containing 1; binding protein; cytokine; dextran sulfate; immunoglobulin enhancer binding protein; lipopolysaccharide; mitogen activated protein kinase; suppressor of cytokine signaling; TAB2 protein; unclassified drug; animal experiment; animal model; Article; ASB1 gene; bacterial infection; C57BL 6 mouse; colitis; controlled study; dextran sulfate sodium-induced colitis; disease severity; gene; human; immunoregulation; infectious agent; MAPK signaling; mouse; nonhuman; priority journal; protein degradation; protein function; protein stability; protein targeting; Salmonella enterica serovar Typhimurium; septic shock; signal transduction; stimulation; survival; ubiquitination
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180972
作者单位	MOE Key Laboratory of Tropical Disease Control, Centre for Infection and Immunity Study, Seventh Affiliated Hospital, School of Medicine, Sun Yat-sen University, Shenzhen, 518107, China; Modern Virology Research Center, College of Life Sciences, Wuhan University, Wuhan, 430072, China; Center for Applied Genomics, Abramson Research Center, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, United States
推荐引用方式 GB/T 7714	Hou P.,Jia P.,Yang K.,et al. An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis[J],2021,118(3).
APA	Hou P..,Jia P..,Yang K..,Li Z..,Tian T..,...&Guo D..(2021).An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis.Proceedings of the National Academy of Sciences of the United States of America,118(3).
MLA	Hou P.,et al."An unconventional role of an ASB family protein in NF-κB activation and inflammatory response during microbial infection and colitis".Proceedings of the National Academy of Sciences of the United States of America 118.3(2021).