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DOI | 10.1038/s41467-018-08275-7 |
The PYRIN domain-only protein POP2 inhibits inflammasome priming and activation | |
Ratsimandresy, Rojo A.1; Chu, Lan H.1,2; Khare, Sonal1,7; de Almeida, Lucia1; Gangopadhyay, Anu1,2; Indramohan, Mohanalaxmi1; Misharin, Alexander V.3; Greaves, David R.4; Perlman, Harris1; Dorfleutner, Andrea1; Stehlik, Christian1,5,6 | |
2019-01-17 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; England; India |
英文摘要 | Inflammasomes are protein platforms linking recognition of microbe, pathogen-associated and damage-associated molecular patterns by cytosolic sensory proteins to caspase-1 activation. Caspase-1 promotes pyroptotic cell death and the maturation and secretion of interleukin (IL)-1 beta and IL-18, which trigger inflammatory responses to clear infections and initiate wound-healing; however, excessive responses cause inflammatory disease. Inflammasome assembly requires the PYRIN domain (PYD)-containing adaptor ASC, and depends on PYD-PYD interactions. Here we show that the PYD-only protein POP2 inhibits inflammasome assembly by binding to ASC and interfering with the recruitment of ASC to upstream sensors, which prevents caspase-1 activation and cytokine release. POP2 also impairs macrophage priming by inhibiting the activation of non-canonical I kappa B kinase epsilon and I kappa B alpha, and consequently protects from excessive inflammation and acute shock in vivo. Our findings advance our understanding of the complex regulatory mechanisms that maintain a balanced inflammatory response and highlight important differences between individual POP members. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000402745700001 |
WOS关键词 | NF-KAPPA-B ; CASPASE RECRUITMENT DOMAIN ; SPECK-LIKE PROTEIN ; NLRP3 INFLAMMASOME ; PATTERN-RECOGNITION ; MICE DEFICIENT ; CUTTING EDGE ; CELL-DEATH ; IN-VIVO ; ASC |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
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/204175 |
专题 | 资源环境科学 |
作者单位 | 1.Northwestern Univ, Feinberg Sch Med, Dept Med, Div Rheumatol, Chicago, IL 60611 USA; 2.Northwestern Univ, Feinberg Sch Med, Driskill Grad Program Life Sci, Chicago, IL 60611 USA; 3.Northwestern Univ, Feinberg Sch Med, Dept Med, Div Pulm & Crit Care, Chicago, IL 60611 USA; 4.Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England; 5.Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Interdept Immunobiol Ctr, Chicago, IL 60611 USA; 6.Northwestern Univ, Feinberg Sch Med, Skin Dis Res Ctr, Chicago, IL 60611 USA; 7.Jubilant Biosys Ltd, 96 Ind Suburb,2nd Stage, Bangalore 560022, Karnataka, India |
推荐引用方式 GB/T 7714 | Ratsimandresy, Rojo A.,Chu, Lan H.,Khare, Sonal,et al. The PYRIN domain-only protein POP2 inhibits inflammasome priming and activation[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Ratsimandresy, Rojo A..,Chu, Lan H..,Khare, Sonal.,de Almeida, Lucia.,Gangopadhyay, Anu.,...&Stehlik, Christian.(2019).The PYRIN domain-only protein POP2 inhibits inflammasome priming and activation.NATURE COMMUNICATIONS,8. |
MLA | Ratsimandresy, Rojo A.,et al."The PYRIN domain-only protein POP2 inhibits inflammasome priming and activation".NATURE COMMUNICATIONS 8(2019). |
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