On Cancer Cell Cycle and Universal Apoptosis Parameters Signaling Unravelled In Silico

Abstract

Here, cell cycle in higher eukaryotes and their molecular networks signals both in G1/S and G2/M transitions are in silico replicated. Systems control theory is employed to design multi-nestled digital layers to simulate protein-toprotein 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) paved the way for unravelling the participants and their by-products having the task to execute (or not) cell death. The results of the proposed cell digital multi-layers give reason to believe in the existence of an universal apoptotic mechanism. 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.