Integrated computational model of cell cycle and checkpoint reveals different essential roles of Aurora-A and Plk1 in mitotic entry
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Updated: Jun 7, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
Jun Zou1, Shi-Dong Luo, Yu-Quan Wei
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Abstract:
Understanding the regulation of mitotic entry is one of the most important goals of modern cell biology, and computational modeling of mitotic entry has been a subject of several recent studies. However, there are still many regulation mechanisms that remain poorly characterized. Two crucial aspects are how mitotic entry is controlled by its upstream regulators Aurora-A and Plk1, and how mitotic entry is coordinated with other biological events, especially G2/M checkpoint. In this context, we reconstructed a comprehensive computational model that integrates the mitotic entry network and the G2/M checkpoint system. Computational simulation of this model and subsequent experimental verification revealed that Aurora-A and Plk1 are redundant to the activation of cyclin B/Cdk1 during normal mitotic entry, but become especially important for cyclin B/Cdk1 activation during G2/M checkpoint recovery. Further analysis indicated that, in response to DNA damage, Chk1-mediated network rewiring makes cyclin B/Cdk1 more sensitive to the down-regulation of Aurora-A and Plk1. In addition, we demonstrated that concurrently targeting Aurora-A and Plk1 during G2/M checkpoint recovery achieves a synergistic effect, which suggests the combinational use of Aurora-A and Plk1 inhibitors after chemotherapy or radiotherapy. Thus, the results presented here provide novel insights into the regulation mechanism of mitotic entry and have potential value in cancer therapy.
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