炎症体
信号转导衔接蛋白
先天免疫系统
细胞生物学
泛素
潮湿
生物
免疫系统
调节器
激活剂(遗传学)
信号转导
化学
炎症
免疫学
受体
生物化学
基因
物理
气象学
作者
Wanxin Zhuang,Lei Zhang,Yi Zheng,Bingyu Liu,Chun Pyo Hong,Wei Zhao,Suxia Liu,Feng Liu,Chengjiang Gao
标识
DOI:10.1038/s41423-022-00917-7
摘要
Inflammasomes are essential components of the innate immune system and its defense against infections, whereas the dysregulation of inflammasome activation has a detrimental effect on human health. The activation of inflammasomes is subjected to tight regulation to maintain immune homeostasis, yet the underlying mechanism remains elusive. Here, we identify USP3 as a direct deubiquitinating enzyme (DUB) for ASC, the central adapter mediating the assembly and activation of most inflammasomes. USP3 removes the K48-linked ubiquitination on ASC and strengthens its stability by blocking proteasomal degradation. Additionally, USP3 promotes inflammasome activation, and this function was confirmed in mouse models of aluminum (Alum)-induced peritonitis, F. novicida infection and flagellin-induced pneumonia in vivo. Our work unveils that USP3 functions as a key regulator of ASC ubiquitination and maintains the physiological role of ASC in mediating inflammasome activation, and we propose a new mechanism by which the ubiquitination of ASC regulates inflammasome activation.
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