Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis

doi:10.1073/pnas.1722013115

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	Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis
	Meng, Huyan 1,4; Liu, Zhen 1; Li, Xingyan 1,4; Wang, Huibing 1,2,4; Jin, Taijie 1,4; Wu, Guowei 1,4; Shan, Bing 1; Christofferson, Dana E.2; Qi, Chunting 3; Yu, Qiang3
刊名	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
	2018-02-27
卷号	115 期号:9 页码:E2001-E2009
关键词	RIPK1 death domain dimerization necroptosis RIPK1-dependent apoptosis
ISSN号	0027-8424
DOI	10.1073/pnas.1722013115
文献子类	Article
英文摘要	RIPK1 is a critical mediator of cell death and inflammation downstream of TNFR1 upon stimulation by TNF alpha, a potent proinflammatory cytokine involved in a multitude of human inflammatory and degenerative diseases. RIPK1 contains an N-terminal kinase domain, an intermediate domain, and a C-terminal death domain (DD). The kinase activity of RIPK1 promotes cell death and inflammation. Here, we investigated the involvement of RIPK1-DD in the regulation of RIPK1 kinase activity. We show that a charge-conserved mutation of a lysine located on the surface of DD (K599R in human RIPK1 or K584R in murine RIPK1) blocks RIPK1 activation in necroptosis and RIPK1-dependent apoptosis and the formation of complex II. Ripk1(K584R/K584R) knockin mutant cells are resistant to RIPK1 kinase-dependent apoptosis and necroptosis. The resistance of K584R cells, however, can be overcome by forced dimerization of RIPK1. Finally, we show that the K584R RIPK1 knockin mutation protects mice against TNF alpha-induced systematic inflammatory response syndrome. Our study demonstrates the role of RIPK1-DD in mediating RIPK1 dimerization and activation of its kinase activity during necroptosis and RIPK1-dependent apoptosis.
资助项目	China National Natural Science Foundation[31530041] ; National Key R&D Program of China[2016YFA0501900] ; Chinese Academy of Sciences[00000000] ; National Institute of Neurological Disorders and Stroke[1R01NS082257] ; National Institute on Aging[1R01AG047231] ; National Institute on Aging[RF1AG055521] ; Natural Science Foundation of Shanghai[16ZR1443900]
WOS关键词	INFLAMMATORY RESPONSE SYNDROME ; NECROSIS-FACTOR RECEPTOR-1 ; CELL-DEATH ; PROGRAMMED NECROSIS ; SIGNALING COMPLEX ; TNF-ALPHA ; KINASE ; PROTEIN ; FADD ; UBIQUITINATION
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATL ACAD SCIENCES
WOS记录号	WOS:000426152500013
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279888]
专题	药理学第一研究室
通讯作者	Li, Ying; Yuan, Junying
作者单位	1.Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201203, Peoples R China; 2.Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
推荐引用方式 GB/T 7714	Meng, Huyan,Liu, Zhen,Li, Xingyan,et al. Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2018,115(9):E2001-E2009.
APA	Meng, Huyan.,Liu, Zhen.,Li, Xingyan.,Wang, Huibing.,Jin, Taijie.,...&Yuan, Junying.(2018).Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,115(9),E2001-E2009.
MLA	Meng, Huyan,et al."Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 115.9(2018):E2001-E2009.