Encoding and Decoding of p53 Dynamics in Cellular Response to Stresses

卷:12

Review

关键词: DNA-DAMAGE RESPONSE;    DEPENDENT PROTEIN-KINASE;    P53-MDM2 FEEDBACK LOOP;    FATE DECISION;    POSTTRANSLATIONAL MODIFICATION;    BASAL DYNAMICS;    PHOSPHORYLATION;    PULSES;    MDM2;    ACTIVATION;   

DOI  :  10.3390/cells12030490

来源: SCIE

【 摘 要 】

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.