Intricate Dynamical Cross-Talk Between p53 Protein and Cell Cycle Regulators Governs Mammalian Cell Fate
Charan, K.; Kar, S.
Show abstract
In mammalian cells, under normal circumstances, the p53 protein exhibits oscillatory dynamics in response to DNA damage and maintains the cells in a cell-cycle-arrested state. Intriguingly, some cells can escape this cell-cycle-arrested state even after prolonged DNA damage, and often undergo mitotic catastrophe. In this context, the precise role of p53 dynamics and its complex interplay with cell-cycle regulation remain poorly understood. Herein, by constructing a comprehensive network model, we have identified crucial crosstalk regulations between the p53 protein and key cell-cycle regulators that enable some cells to escape cell-cycle arrest during prolonged DNA damage. The model further illustrates a probable cellular mechanism underlying mitotic catastrophe and predicts ways to induce it in a therapeutically relevant manner.
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