R. M. Ardito Marretta^*, F. Ales^†

Molecular & Cellular Biomechanics, Vol.7, No.4, pp. 225-266, 2010, DOI:10.3970/mcb.2010.007.225

Abstract In this paper, cell cycle in higher eukaryotes and their molecular networks signals both inG1/SandG2/Mtransitions are replicatedin silico. Biochemical kinetics, converted into a set of differential equations, and system control theory are employed to design multi-nested digital layers to simulate protein-to-protein activation and inhibition for cell cycle dynamics in the presence of damaged genomes. 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 allows the comprehension of the mechanisms of these molecule interactions but paves the way for unraveling the participants and their by-products, until… More >

R. M. Ardito Marretta^∗,†, G. Barbaraci^‡

Molecular & Cellular Biomechanics, Vol.7, No.3, pp. 135-164, 2010, DOI:10.3970/mcb.2010.007.135

Abstract Upon severe DNA damage, p21 acts in a dual mode; on the one hand, it inhibits the cyclin-CDK complex for arresting the G2/M transition and on the other hand, it indirectly becomes an apoptotic factor by activating - in sequence - the retinoblastoma protein, E2F1 and APAF1 expressions. But, in a cancer cells proliferation, the mechanisms of, and participants in, the apoptosis failure remain unclear. Since the p21/p53/Mdm2 proteins network normally involves a digital response in a cancer cell, through an original design of a cell signalling-protein simulator, we demonstrate,in silico, that apoptosis phase instability is fully reciprocated by p21mRNA… More >

R. M. Ardito Marretta^*, G. Barbaraci^†

Molecular & Cellular Biomechanics, Vol.6, No.3, pp. 175-190, 2009, DOI:10.3970/mcb.2009.006.175

Abstract This study, through a typical aerospace systems architecture, suggests an engineering design of a human cancer cell circuitry in which a digital optimal control matrix is assigned to repair the DNA damage level and/or to trigger its apoptosis.
Here, the conceived machinery is proposed taking into account the state of the art in cancer investigation. However, it could be further generalized. The most recent studies on cancer pathologies give a predominant role to the oncosuppressor protein p53 and its antagonist, the oncogene Mdm2.
Experimental and theoretical approaches are in agreement in deducing a “digital” response of the p53 when genomic… More >