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RIP3-mediated necroptosis is regulated by inter-filament assembly of RIP homotypic interaction motif | |
2021-01 | |
Source Publication | CELL DEATH AND DIFFERENTIATION
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ISSN | 1350-9047 |
EISSN | 1476-5403 |
Status | 已发表 |
DOI | 10.1038/s41418-020-0598-9 |
Abstract | Necroptosis is mediated by signaling complexes called necrosomes, which contain receptor-interacting protein 3 (RIP3) and upstream effectors, such as RIP1. In necrosomes, the RIP homotypic interaction motif (RHIM) of RIP3 and RIP1 forms amyloidal complex. But how the amyloidal necrosomes control RIP3 activation and cell necroptosis has not been determined. Here, we showed that RIP3 amyloid fibrils could further assemble into large fibrillar networks which presents as cellular puncta during necroptosis. A viral RHIM-containing necroptosis inhibitor M45 could form heteroamyloid with RIP3 in cells and prevent RIP3 puncta formation and cell necroptosis. We characterized mutual antagonism between RIP3–RHIM and M45–RHIM in necroptosis regulation, which was caused by distinct inter-filament interactions in RIP3, M45 amyloids revealed with atomic force microscopy. Moreover, double mutations Asn464 and Met468 in RIP3–RHIM to Asp disrupted RIP3 kinase-dependent necroptosis. While the mutant RIP3(N464D/M468D) could form amyloid as wild type upon necroptosis induction. Based on these results, we propose that RIP3 amyloid formation is required but not sufficient in necroptosis signaling, the ordered inter-filament assembly of RIP3 is critical in RIP3 amyloid mediated kinase activation and cell necroptosis. |
URL | 查看原文 |
Indexed By | SCI ; SCIE |
Funding Project | Analytical Instrumentation Center, SPST, ShanghaiTech University[SPST-AIC10112914] ; National Natural Science Foundation of China[31770790][31571427] |
WOS Research Area | Biochemistry & Molecular Biology ; Cell Biology |
WOS Subject | Biochemistry & Molecular Biology ; Cell Biology |
WOS ID | WOS:000554349600003 |
Publisher | NATURE PUBLISHING GROUP |
WOS Keyword | PROGRAMMED NECROSIS ; CELL-DEATH ; VIRUS ; CYTOMEGALOVIRUS ; INFLAMMATION |
Original Document Type | Article |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/122495 |
Collection | 生命科学与技术学院 生命科学与技术学院_PI研究组_王华翌组 生命科学与技术学院_PI研究组_陆珺霞组 生命科学与技术学院_公共科研平台_分子细胞学平台 生命科学与技术学院_硕士生 生命科学与技术学院_博士生 |
Co-First Author | Wu, Xialian |
Corresponding Author | Lu, Junxia; Wang, Huayi |
Affiliation | 1.ShanghaiTech Univ, Sch Life Sci & Technol, 393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100864, Peoples R China |
First Author Affilication | School of Life Science and Technology |
Corresponding Author Affilication | School of Life Science and Technology |
First Signature Affilication | School of Life Science and Technology |
Recommended Citation GB/T 7714 | Hu, Hong,Wu, Xialian,Wu, Guoxiang,et al. RIP3-mediated necroptosis is regulated by inter-filament assembly of RIP homotypic interaction motif[J]. CELL DEATH AND DIFFERENTIATION,2021. |
APA | Hu, Hong.,Wu, Xialian.,Wu, Guoxiang.,Nan, Ning.,Zhang, Jing.,...&Wang, Huayi.(2021).RIP3-mediated necroptosis is regulated by inter-filament assembly of RIP homotypic interaction motif.CELL DEATH AND DIFFERENTIATION. |
MLA | Hu, Hong,et al."RIP3-mediated necroptosis is regulated by inter-filament assembly of RIP homotypic interaction motif".CELL DEATH AND DIFFERENTIATION (2021). |
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