坏死性下垂
生物
肿瘤坏死因子α
细胞生物学
程序性细胞死亡
效应器
基因敲除
坏死
细胞凋亡
p38丝裂原活化蛋白激酶
基因剔除小鼠
激酶
MAPK/ERK通路
免疫学
基因
遗传学
作者
Jianfeng Wu,Zhenguo Huang,Junming Ren,Zhirong Zhang,Peng He,Yangxin Li,Jian Ma,Wanze Chen,Yingying Zhang,Xiaojuan Zhou,Zhentao Yang,Shuodong Wu,Lanfen Chen,Jiahuai Han
出处
期刊:Cell Research
[Springer Nature]
日期:2013-07-09
卷期号:23 (8): 994-1006
被引量:378
摘要
Mixed lineage kinase domain-like protein (Mlkl) was recently found to interact with receptor interacting protein 3 (Rip3) and to be essential for tumor necrosis factor (TNF)-induced programmed necrosis (necroptosis) in cultured cell lines. We have generated Mlkl-deficient mice by transcription activator-like effector nucleases (TALENs)-mediated gene disruption and found Mlkl to be dispensable for normal mouse development as well as immune cell development. Mlkl-deficient mouse embryonic fibroblasts (MEFs) and macrophages both showed resistance to necrotic but not apoptotic stimuli. Mlkl-deficient MEFs and macrophages were indistinguishable from wild-type cells in their ability to activate NF-κB, ERK, JNK, and p38 in response to TNF and lipopolysaccharides (LPS), respectively. Consistently, Mlkl-deficient macrophages and mice exhibited normal interleukin-1β (IL-1β), IL-6, and TNF production after LPS treatment. Mlkl deficiency protects mice from cerulean-induced acute pancreatitis, a necrosis-related disease, but has no effect on polymicrobial septic shock-induced animal death. Our results provide genetic evidence for the role of Mlkl in necroptosis.
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