NF-kappa B signaling and cell-fate decision induced by a   fast-dissociating tumor necrosis factor mutant

doi:10.1016/j.bbrc.2017.05.149

CORC > 北京大学 > 化学与分子工程学院

	NF-kappa B signaling and cell-fate decision induced by a fast-dissociating tumor necrosis factor mutant
	Zhang, Xiaoling ; Yin, Ning ; Guo, Annan ; Zhang, Qi ; Zhang, Yalei ; Xu, Youjun ; Liu, Hongbo ; Tang, Bo ; Lai, Luhua
刊名	BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
	2017
关键词	NF-kappa B signaling dynamics TNF Receptor-ligand binding kinetics Gene expression Biased activation Apoptosis GENE-EXPRESSION DYNAMICS SPECIFICITY DETERMINES KINETICS ALPHA TNF
DOI	10.1016/j.bbrc.2017.05.149
英文摘要	Tumor necrosis factor (TNF) is a pluripotent inflammatory cytokine that can induce both the pro-survival nuclear factor kappa B (NF-KB) pathway and the pro-apoptotic caspase pathway. Selectively activating only one of the two pathways remains challenging. We used TNF mutants with different receptor binding kinetics to study their effects on NF-KB signaling dynamics and cell apoptosis. A TNF mutant, R1antTNF, which binds to TNFR1 with increased association and dissociation rates, induced NF-KB signaling with shorter response time and first peak duration. The short nuclear stay of NF-KB led to biased activation of downstream genes, favoring the fast response ones. At the same time, R1antTNF retains pro-apoptotic activity. At 10 ng/ml, R1antTNF selectively activated the pro-apoptotic pathway rather than the pro survival NF-KB pathway. Our study provides a new example for the emerging evidence that ligand-receptor binding kinetics play a key role in the selective activation of downstream pathways, which deserves more attention in future drug discovery and disease studies. (C) 2017 Elsevier Inc. All rights reserved.; Ministry of Science and Technology of China [2015CB910300, 2016YFA0502303]; National Natural Science Foundation of China [21633001]; SCI(E); ARTICLE; 3; 287-292; 489
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/471991]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Zhang, Xiaoling,Yin, Ning,Guo, Annan,et al. NF-kappa B signaling and cell-fate decision induced by a fast-dissociating tumor necrosis factor mutant[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2017.
APA	Zhang, Xiaoling.,Yin, Ning.,Guo, Annan.,Zhang, Qi.,Zhang, Yalei.,...&Lai, Luhua.(2017).NF-kappa B signaling and cell-fate decision induced by a fast-dissociating tumor necrosis factor mutant.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.
MLA	Zhang, Xiaoling,et al."NF-kappa B signaling and cell-fate decision induced by a fast-dissociating tumor necrosis factor mutant".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2017).