Abstract:
In the cellular response to stresses, the tumor suppressor p53 is activated to maintain genomic integrity and fidelity. As a transcription factor, p53 exhibits rich dynamics to allow for discrimination of the type and intensity of stresses and to direct the selective activation of target genes involved in different processes including cell cycle arrest and apoptosis. In this review, we focused on how stresses are encoded into p53 dynamics and how the dynamics are decoded into cellular outcomes. Theoretical modeling may provide a global view of signaling in the p53 network by coupling the encoding and decoding processes. We discussed the significance of modeling in revealing the mechanisms of the transition between p53 dynamic modes. Moreover, we shed light on the crosstalk between the p53 network and other signaling networks. This review may advance the understanding of operating principles of the p53 signaling network comprehensively and provide insights into p53 dynamics-based cancer therapy.
摘要:
在细胞对压力的反应中,肿瘤抑制因子p53被激活以维持基因组的完整性和保真度。作为转录因子,p53表现出丰富的动力学,可以区分应激的类型和强度,并指导参与不同过程(包括细胞周期停滞和凋亡)的靶基因的选择性激活。在这次审查中,我们关注的是应力如何被编码成p53动力学,以及该动力学如何被解码成细胞结果.理论建模可以通过耦合编码和解码过程来提供p53网络中信号传导的全局视图。我们讨论了建模在揭示p53动态模式之间过渡机制中的意义。此外,我们揭示了p53网络和其他信号网络之间的串扰。这篇综述可以全面推进对p53信号网络工作原理的理解,并为基于p53动力学的癌症治疗提供见解。