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DOI | 10.1126/science.aau1330 |
Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes | |
Sandstrom, Andrew1,2,3; Mitchell, Patrick S.1,2; Goers, Lisa4,5,6; Mu, Edward W.1,2; Lesser, Cammie F.4,5,6; Vance, Russell E.1,2,3 | |
2019-04-05 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6435页码:42-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | Inflammasomes are multiprotein platforms that initiate innate immunity by recruitment and activation of caspase-1. The NLRP1B inflammasome is activated upon direct cleavage by the anthrax lethal toxin protease. However, the mechanism by which cleavage results in NLRP1B activation is unknown. In this study, we find that cleavage results in proteasome-mediated degradation of the amino-terminal domains of NLRP1B, liberating a carboxyl-terminal fragment that is a potent caspase-1 activator. Proteasome-mediated degradation of NLRP1B is both necessary and sufficient for NLRP1B activation. Consistent with our functional degradation model, we identify IpaH7.8, a Shigella flexneri ubiquitin ligase secreted effector, as an enzyme that induces NLRP1B degradation and activation. Our results provide a unified mechanism for NLRP1B activation by diverse pathogen-encoded enzymatic activities. |
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:000463585700027 |
WOS关键词 | ANTHRAX LETHAL TOXIN ; CASPASE-1 ACTIVATION ; UBIQUITIN LIGASES ; RHO GTPASES ; CELL-DEATH ; PROTEIN ; MOUSE ; SUSCEPTIBILITY ; RECOGNITION ; BACTERIA |
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/201136 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol & Pathogenesis, 229 Stanley Hall, Berkeley, CA 94720 USA; 2.Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA; 3.Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA; 4.Harvard Med Sch, Dept Microbiol, Boston, MA 02115 USA; 5.Broad Inst MIT & Harvard, Cambridge, MA 02142 USA; 6.Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA |
推荐引用方式 GB/T 7714 | Sandstrom, Andrew,Mitchell, Patrick S.,Goers, Lisa,et al. Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes[J]. SCIENCE,2019,364(6435):42-+. |
APA | Sandstrom, Andrew,Mitchell, Patrick S.,Goers, Lisa,Mu, Edward W.,Lesser, Cammie F.,&Vance, Russell E..(2019).Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes.SCIENCE,364(6435),42-+. |
MLA | Sandstrom, Andrew,et al."Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes".SCIENCE 364.6435(2019):42-+. |
条目包含的文件 | 条目无相关文件。 |
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