炎症体
目标2
泛素
细胞生物学
上睑下垂
脱氮酶
半胱氨酸蛋白酶1
生物
NLRC4型
先天免疫系统
化学
自噬
炎症
免疫系统
生物化学
免疫学
基因
作者
Yujin Hong,Seong-Ok Lee,Changhoon Oh,Kwonyoon Kang,Jeongmin Ryoo,Dong‐Young Kim,Kwangseog Ahn
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2021-10-01
卷期号:207 (7): 1926-1936
被引量:8
标识
DOI:10.4049/jimmunol.2100449
摘要
Innate immune sensing of cytosolic DNA via absent in melanoma 2 (AIM2) is a key mechanism leading to inflammatory responses. As aberrant immune responses by dysregulated AIM2 are associated with autoinflammatory diseases, activation of the AIM2 inflammasome should be tightly controlled. In this study, we discovered that ubiquitination and deubiquitination of AIM2 are critical events that regulate AIM2 inflammasome activation. In resting human macrophage cells, AIM2 is constitutively ubiquitinated and undergoes proteasomal degradation to avoid autoinflammation. Upon DNA stimulation, USP21 binds to AIM2 and deubiquitinates it, thereby increasing its protein stability. In addition to the role of USP21 in regulating AIM2 turnover, we uncovered that USP21-mediated deubiquitination of AIM2 is required for the assembly of the AIM2 inflammasome. Depletion of USP21 does not affect the DNA-binding ability of AIM2 but inhibits the formation of the AIM2-ASC complex. Our findings establish that fine-tuning of AIM2 by the ubiquitin system is important for regulating AIM2 inflammasome activation.
科研通智能强力驱动
Strongly Powered by AbleSci AI