Kuang Yaming Honors School, Nanjing University, Nanjing 210023, China.
Key Laboratory of High Performance Scientific Computation, School of Science, Xihua University, Chengdu 610039, China.
Cells. 2023 Feb 2;12(3):490. doi: 10.3390/cells12030490.
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.
在细胞应对压力的过程中,肿瘤抑制因子 p53 被激活以维持基因组的完整性和保真度。作为一种转录因子,p53 表现出丰富的动力学特性,以允许区分压力的类型和强度,并指导参与不同过程(包括细胞周期停滞和细胞凋亡)的靶基因的选择性激活。在这篇综述中,我们重点讨论了压力如何编码为 p53 动力学,以及动力学如何解码为细胞结果。通过将编码和解码过程相结合,理论建模可以为 p53 网络中的信号提供全局视图。我们讨论了建模在揭示 p53 动态模式之间转变的机制方面的重要性。此外,我们还探讨了 p53 网络与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新的见解。