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DOI | 10.1126/science.aaw4144 |
The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling | |
Abdel-Nour, Mena1; Carneiro, Leticia A. M.1,8; Downey, Jeffrey2; Tsalikis, Jessica1; Outlioua, Ahmed3,4; Prescott, Dave1,5; Da Costa, Leandro Silva3; Hovingh, Elise S.1; Farahvash, Armin1; Gaudet, Ryan G.6; Molinaro, Raphael1; van Dalen, Rob1,9; Lau, Charles C. Y.1,5; Azimi, Farshad C.1; Escalante, Nichole K.5,10; Trotman-Grant, Aaron5; Lee, Jeffrey E.1; Gray-Owen, Scott D.6; Divangahi, Maziar2; Chen, Jane-Jane7; Philpott, Dana J.5; Arnoult, Damien3; Girardin, Stephen E.1 | |
2019-07-05 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 365期号:6448页码:47-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Canada; France; Morocco; USA; Brazil; Germany |
英文摘要 | Multiple cytosolic innate sensors form large signalosomes after activation, but this assembly needs to be tightly regulated to avoid accumulation of misfolded aggregates. We found that the eIF2a kinase heme-regulated inhibitor (HRI) controls NOD1 signalosome folding and activation through a process requiring eukaryotic initiation factor 2 alpha (eIF2 alpha), the transcription factor ATF4, and the heat shock protein HSPB8. The HRI/eIF2 alpha signaling axis was also essential for signaling downstream of the innate immune mediators NOD2, MAVS, and TRIF but dispensable for pathways dependent on MyD88 or STING. Moreover, filament-forming a-synuclein activated HRI-dependent responses, which suggests that the HRI pathway may restrict toxic oligomer formation. We propose that HRI, eIF2 alpha, and HSPB8 define a novel cytosolic unfolded protein response (cUPR) essential for optimal innate immune signaling by large molecular platforms, functionally homologous to the PERK/eIF2 alpha/HSPA5 axis of the endoplasmic reticulum UPR. |
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:000474432700029 |
WOS关键词 | TRANSLATIONAL CONTROL ; EIF2-ALPHA KINASE ; ALPHA-SYNUCLEIN ; PHOSPHORYLATION ; ACTIVATION ; NOD1 ; HRI ; SURVIVAL ; DEFENSE |
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/201800 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada; 2.McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada; 3.Hop Paul Brousse, INSERM, U1197, Batiment Lavoisier, F-94807 Villejuif, France; 4.Hassan II Univ Casablanca, Ain Chock Fac Sci, Hlth & Environm Lab, Mol Genet & Immunophysiopathol Res Team, Casablanca, Morocco; 5.Univ Toronto, Dept Immunol, Toronto, ON, Canada; 6.Univ Toronto, Dept Mol Genet, Toronto, ON, Canada; 7.MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA; 8.Univ Fed Rio de Janeiro, Inst Microbiol, Rio De Janeiro, Brazil; 9.Univ Tubingen, Interfac Inst Microbiol & Infect Med, Infect Biol, Tubingen, Germany; 10.Stanford Univ, Dept Pathol, Palo Alto, CA 94304 USA |
推荐引用方式 GB/T 7714 | Abdel-Nour, Mena,Carneiro, Leticia A. M.,Downey, Jeffrey,et al. The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling[J]. SCIENCE,2019,365(6448):47-+. |
APA | Abdel-Nour, Mena.,Carneiro, Leticia A. M..,Downey, Jeffrey.,Tsalikis, Jessica.,Outlioua, Ahmed.,...&Girardin, Stephen E..(2019).The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling.SCIENCE,365(6448),47-+. |
MLA | Abdel-Nour, Mena,et al."The heme-regulated inhibitor is a cytosolic sensor of protein misfolding that controls innate immune signaling".SCIENCE 365.6448(2019):47-+. |
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