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c-Jun N-terminal kinases differentially regulate TNF- and TLRs-mediated necroptosis through their kinase-dependent and -independent activities

文献类型：期刊论文

作者Cao, Mengtao5,6; Chen, Fei5,6; Xie, Ni5; Chen, Pengfei5; Lou, Qi5,6; Zhao, Yanli5; Mou, Lisha5; Gao, Hanchao3,5; Sun, Yu6; Cao, Meng-Yao1
刊名CELL DEATH & DISEASE
出版日期2018
卷号9期号:-页码:1140
ISSN号2041-4889
关键词CTLA-4 Psoriasis T cells Mouse model of psoriasis
DOI10.1038/s41419-018-1189-2
文献子类Article
英文摘要Tumor necrosis factor (TNF) and Toll-like receptor (TLR) 3/TLR4 activation trigger necroptotic cell death through downstream signaling complex containing receptor-interacting protein kinase 1 (RIPK1), RIPK3, and pseudokinase mixed lineage kinase-domain-like (MLKL). However, the regulation of necroptotic signaling pathway is far less investigated. Here we showed that c-Jun N-terminal kinases (JNK1 and JNK2) displayed kinase-dependent and -independent functions in regulating TNF- and TLRs-mediated necroptosis. We found that RIPK1 and RIPK3 promoted cell-death-independent JNK activation in macrophages, which contributed to pro-inflammatory cytokines production. Meanwhile, blocking the kinase activity of JNK dramatically reduced TNF and TLRs-induced necroptotic cell death. Consistently, inhibition of JNK activity protected mice from TNF-induced death and Staphylococcus aureus-mediated lung damage. However, depletion of JNK protein using siRNA sensitized macrophages to necroptosis that was triggered by LPS or poly I: C but still inhibited TNF-induced necroptosis. Mechanistic studies revealed that RIPK1 recruited JNK to the necrosome complex and their kinase activity was required for necrosome formation and the phosphorylation of MLKL in TNF- and TLRs-induced necroptosis. Loss of JNK protein consistently suppressed the phosphorylation of MLKL and necrosome formation in TNF-triggered necroptosis, but differentially promoted the phosphorylation of MLKL and necrosome formation in poly I: C-triggered necroptosis by promoting the oligomeration of TRIF. In conclusion, our findings define a differential role for JNK in regulating TNF- and TLRs-mediated necroptosis by their kinase or scaffolding activities.
学科主题Cell Biology
WOS关键词MIXED LINEAGE KINASE ; INDUCED CELL-DEATH ; PROGRAMMED NECROSIS ; DOMAIN-LIKE ; KAPPA-B ; PROTEIN-KINASES ; RIPK1 ; INFLAMMATION ; PHOSPHORYLATION ; ACTIVATION
语种英语
出版者NATURE PUBLISHING GROUP
WOS记录号WOS:000450152300003
版本出版稿
源URL[http://202.127.25.144/handle/331004/859]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Peoples Hosp Tongliang Dist, Dept Radiol, Chongqing 402560, Peoples R China;
2.Shenzhen Univ, Dept Ophthalmol, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Shenzhen 518035, Guangdong, Peoples R China;
3.Guangdong Med Univ, Dept Nephrol, Shenzhen Longhua Dist Cent Hosp, Affiliated Longhua Dist Cent Hosp, Shenzhen 518300, Peoples R China;
4.Harvard Med Sch, Div Immunol, Dept Microbiol & Immunobiol, Boston, MA 02115 USA;
5.Shenzhen Univ, Inst Transformat Med, Shenzhen Peoples Hosp 2, Affiliated Hosp 1,Sch Med, Shenzhen 518300, Peoples R China;
6.Chinese Acad Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai Inst Biol Sci,Univ Chinese Acad Sci, Shanghai 200031, Peoples R China;
7.Shenzhen Univ, Dept Sports Med, Shenzhen Peoples Hosp 2, Affiliated Hosp 1, Shenzhen 518035, Guangdong, Peoples R China,
推荐引用方式
GB/T 7714		 Cao, Mengtao,Chen, Fei,Xie, Ni,et al. c-Jun N-terminal kinases differentially regulate TNF- and TLRs-mediated necroptosis through their kinase-dependent and -independent activities[J]. CELL DEATH & DISEASE,2018,9(-):1140.
APA Cao, Mengtao.,Chen, Fei.,Xie, Ni.,Chen, Pengfei.,Lou, Qi.,...&,.(2018).c-Jun N-terminal kinases differentially regulate TNF- and TLRs-mediated necroptosis through their kinase-dependent and -independent activities.CELL DEATH & DISEASE,9(-),1140.
MLA Cao, Mengtao,et al."c-Jun N-terminal kinases differentially regulate TNF- and TLRs-mediated necroptosis through their kinase-dependent and -independent activities".CELL DEATH & DISEASE 9.-(2018):1140.

入库方式： OAI收割

来源：上海营养与健康研究所

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