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学科主题基础医学
A trigger model of apoptosis induced by tumor necrosis factor signaling
Gu, Chang2; Zhang, Junjie3; Chen, Yingyu4,5; Lei, Jinzhi1
刊名BMC SYSTEMS BIOLOGY
2011-06-20
DOI10.1186/1752-0509-5-S1-S13
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
WOS记录号WOS:000297313700012
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被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
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条目标识符http://ir.bjmu.edu.cn/handle/400002259/54491
专题北京大学基础医学院_免疫学系
北京大学基础医学院
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
推荐引用方式
GB/T 7714
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).
APA Gu, Chang,Zhang, Junjie,Chen, Yingyu,&Lei, Jinzhi.(2011).A trigger model of apoptosis induced by tumor necrosis factor signaling.BMC SYSTEMS BIOLOGY,suppl.1(0).
MLA Gu, Chang,et al."A trigger model of apoptosis induced by tumor necrosis factor signaling".BMC SYSTEMS BIOLOGY suppl.1.0(2011).
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