Session Speaker

On Cancer Cell Cycle and Universal Apoptosis Parameters Signaling Unravelled in Silico
Rosario M Ardito Marretta and Filippo Ales
Italy

Here, cell cycle in higher eukaryotes and their molecular networks signals both in G1/S and G2/M transitions are in silico replicated. Biochemical kinetics, converted into a set of differential equations, and systems control theory are employed to design multi-nestled digital layers to simulate protein-to-protein activation and inhibition in the cancer cell cycle dynamics in presence of damaged genome.

Sequencing and controlling the digital process of four micro-scale species networks (p53/Mdm2/DNA damage; p21mRNA/cyclin-CDK complex; CDK/CDC25/wee1/SKP2/APC/CKI and apoptosis target genes system) not only allow the comprehension of the mechanisms of these molecules networks interactions but it paved the way for unraveling the participants and their by-products - until now almost unclear - having the task to execute (or not) cell death.

Whatever the running simulations are (e.g., different species signals, mutant cells and different DNA damage levels), the results of the proposed cell digital multi-layers give reason to believe in the existence of an universal apoptotic mechanism. As a consequence, we identified and selected cell checkpoints, sizers, timers and specific target genes dynamics both for influencing mitotic process and avoiding cancer proliferation as much as for leading the cancer cell(s) to collapse into a steady stable apoptosis phase.