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

文献类型：期刊论文

作者Meng, Huyan1,4; Liu, Zhen1; Li, Xingyan1,4; Wang, Huibing1,2,4; Jin, Taijie1,4; Wu, Guowei1,4; Shan, Bing1; Christofferson, Dana E.2; Qi, Chunting3; Yu, Qiang3
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期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
DOI10.1073/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.
WOS关键词INFLAMMATORY RESPONSE SYNDROME ; NECROSIS-FACTOR RECEPTOR-1 ; CELL-DEATH ; PROGRAMMED NECROSIS ; SIGNALING COMPLEX ; TNF-ALPHA ; KINASE ; PROTEIN ; FADD ; UBIQUITINATION
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研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000426152500013
出版者NATL ACAD SCIENCES
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.

入库方式： OAI收割

来源：上海药物研究所

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