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学科主题: 基础医学
题名:
A trigger model of apoptosis induced by tumor necrosis factor signaling
作者: Gu, Chang2; Zhang, Junjie3; Chen, Yingyu4,5; Lei, Jinzhi1
刊名: BMC SYSTEMS BIOLOGY
发表日期: 2011-06-20
DOI: 10.1186/1752-0509-5-S1-S13
卷: suppl.1, 期:0
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Mathematical & Computational Biology
研究领域[WOS]: Mathematical & Computational Biology
关键词[WOS]: P53-INDUCED APOPTOSIS ; CASPASE-3 ACTIVATION ; RECEPTOR ; DEATH ; BISTABILITY ; CD95 ; DEGRADATION ; INHIBITION ; PROTEINS ; EVENTS
英文摘要:

Background: The ability of living cells to respond appropriately to apoptosis signals is crucial for the proper development and homeostasis of multicellular organisms. For example, viable cells must be stable enough to appropriately respond to apoptosis signaling so that an irreversible death program is only induced when apoptosis signaling reaches a certain threshold. Previous studies have introduced bistability models in which signaling by caspase-3 activity represents a key regulator of cell fate in response to apoptosis stimuli.

Results: In this study, apoptosis induced by tumor necrosis factor (TNF) signaling is investigated, and a mathematical model without the requirement for bistability is proposed. In this model, rapid degradation of the active forms of caspases -8 and -3 are included, and TNF-signaling is found to induce a pulse of caspase-3 activation and trigger an irreversible death program. This result agrees with experimental observations. The ability of a cell to respond to, or resist, apoptosis stimuli is also discussed. Furthermore, the activation efficiencies of caspases -8 and -3 that are essential to a cell′s response to extracellular apoptosis stimuli are defined. Based on the simulations performed, it is observed that activation efficiencies must be sufficiently sensitive to appropriately compromise a cell′s resistance and effectiveness in response to apoptosis stimuli.

Conclusions: Our results suggest that bistability may not be a necessary condition for the induction of apoptosis by TNF signaling. Rather, a sharp increase in caspase-3 activity might be sufficient to trigger the induction of an irreversible death program. Accordingly, regulation of caspase activity and degradation of active caspases is essential for a cell′s response to apoptosis stimuli.

语种: 英语
所属项目编号: 2011CB910103 ; 30771057 ; 10971113
项目资助者: National Key Project for Basic Research of China(973) ; National Natural Science Foundation of China
WOS记录号: WOS:000297313700012
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54491
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Peking Univ, Sch Math Sci, Beijing 100871, Peoples R China
2.Tsinghua Univ, Zhou Pei Yuan Ctr Appl Math, Beijing 100084, Peoples R China
3.Beijing Normal Univ, Coll Life Sci, Inst Cell Biol, Key Lab Cell Proliferat & Regulat Biol,Minist Edu, Beijing 100875, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Lab Med Immunol, Beijing 100083, Peoples R China
5.Peking Univ, Ctr Human Dis Genom, Beijing 100083, Peoples R China

Recommended Citation:
Gu, Chang,Zhang, Junjie,Chen, Yingyu,et al. A trigger model of apoptosis induced by tumor necrosis factor signaling[J]. BMC SYSTEMS BIOLOGY,2011,suppl.1(0).
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