单细胞中p53动力学建模的最新进展与开放性挑战
Recent progress and open challenges in modeling p53 dynamics in single cells.
作者信息
Batchelor Eric, Loewer Alexander
机构信息
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, MSC 1500, Bethesda, MD 20892, USA.
Department of Biology, Technische Universität Darmstadt, Schnittspahnstrasse 13, 64287 Darmstadt, Germany.
出版信息
Curr Opin Syst Biol. 2017 Jun;3:54-59. doi: 10.1016/j.coisb.2017.04.007. Epub 2017 Mar 25.
Abstract
In mammalian cells, the tumor suppressor p53 is activated upon a variety of cellular stresses and ensures an appropriate response ranging from arrest and repair to the induction of senescence and apoptosis. Quantitative measurements in individual living cells showed stimulus-dependent dynamics of p53 accumulation upon stress induction. Due to the complexity of the underlying biochemical interactions, mathematical models were indispensable for understanding the topology of the network regulating p53 dynamics. Recent work provides furhter insights into the causes of heterogeneous responses in individual cells, the rewiring of the network in response to different inputs and the role of the downstream processes in determining the cellular fate upon stress.
摘要
在哺乳动物细胞中，肿瘤抑制因子p53在多种细胞应激情况下被激活，并确保细胞做出从停滞和修复到衰老和凋亡诱导的适当反应。对单个活细胞的定量测量显示，应激诱导后p53积累呈现出刺激依赖性动态变化。由于潜在生化相互作用的复杂性，数学模型对于理解调节p53动态变化的网络拓扑结构必不可少。最近的研究进一步揭示了单个细胞中异质性反应的原因、网络对不同输入的重新布线以及下游过程在决定应激后细胞命运中的作用。
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本文引用的文献
1
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Mol Biol Cell. 2016 Aug 1;27(15):2360-7. doi: 10.1091/mbc.E16-01-0032. Epub 2016 Jun 8.
2
p53 Pulses Diversify Target Gene Expression Dynamics in an mRNA Half-Life-Dependent Manner and Delineate Co-regulated Target Gene Subnetworks.p53 脉冲以依赖于 mRNA 半衰期的方式使靶基因表达动力学多样化，并描绘出共同调控的靶基因子网络。
Cell Syst. 2016 Apr 27;2(4):272-82. doi: 10.1016/j.cels.2016.03.006. Epub 2016 Apr 7.
3
Cell-to-Cell Variation in p53 Dynamics Leads to Fractional Killing.p53动力学中的细胞间差异导致部分杀伤。
Cell. 2016 Apr 21;165(3):631-42. doi: 10.1016/j.cell.2016.03.025. Epub 2016 Apr 7.
4
MiR-192-Mediated Positive Feedback Loop Controls the Robustness of Stress-Induced p53 Oscillations in Breast Cancer Cells.MiR-192介导的正反馈回路控制乳腺癌细胞应激诱导的p53振荡的稳健性。
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5
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6
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