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DOI | 10.1126/science.aau1208 |
N-terminal degradation activates the NLRP1B inflammasome | |
Chui, Ashley J.1; Okondo, Marian C.2; Rao, Sahana D.1; Gai, Kuo2; Griswold, Andrew R.3; Johnson, Darren C.1; Ball, Daniel P.2; Taabazuing, Cornelius Y.2; Orth, Elizabeth L.1; Vittimberga, Brooke A.2; Bachovchin, Daniel A.1,2,3 | |
2019-04-05 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6435页码:82-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptosis. The anthrax lethal factor metalloprotease and small-molecule DPP8/9 inhibitors both activate the NLRP1B inflammasome, but the molecular mechanism of NLRP1B activation is unknown. In this study, we used genome-wide CRISPR-Cas9 knockout screens to identify genes required for NLRP1B-mediated pyroptosis. We discovered that lethal factor induces cell death via the N-end rule proteasomal degradation pathway. Lethal factor directly cleaves NLRP1B, inducing the N-end rule-mediated degradation of the NLRP1B N terminus and freeing the NLRP1B C terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the NLRP1B N terminus but not via the N-end rule pathway. Thus, N-terminal degradation is the common activation mechanism of this innate immune sensor. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000463585700038 |
WOS关键词 | ANTHRAX LETHAL TOXIN ; END RULE PATHWAY ; INHIBITION ; CYTOTOXICITY |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201137 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Mem Sloan Kettering Canc Ctr, Triinst PhD Program Chem Biol, New York, NY 10065 USA; 2.Mem Sloan Kettering Canc Ctr, Chem Biol Program, New York, NY 10065 USA; 3.Mem Sloan Kettering Canc Ctr, Weill Cornell Grad Sch Med Sci, Pharmacol Program, New York, NY 10065 USA |
推荐引用方式 GB/T 7714 | Chui, Ashley J.,Okondo, Marian C.,Rao, Sahana D.,et al. N-terminal degradation activates the NLRP1B inflammasome[J]. SCIENCE,2019,364(6435):82-+. |
APA | Chui, Ashley J..,Okondo, Marian C..,Rao, Sahana D..,Gai, Kuo.,Griswold, Andrew R..,...&Bachovchin, Daniel A..(2019).N-terminal degradation activates the NLRP1B inflammasome.SCIENCE,364(6435),82-+. |
MLA | Chui, Ashley J.,et al."N-terminal degradation activates the NLRP1B inflammasome".SCIENCE 364.6435(2019):82-+. |
条目包含的文件 | 条目无相关文件。 |
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