Digital control circuitry of cancer cell and its apoptosis.
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 integrity is damaged. Once DNA damage is present, the mutual influence of p53 and its antagonist, the Mdm2 oncogene, is closed in a feedback loop. In this work, starting from these current results, a novel molecular mechanism is proposed, based on a digital optimal control law, whereby p53 and Mdm2 proteins activities can be represented by appropriate circuitry and governed by the optimal control law of digital systems. This procedure obtains a real-time sequence evaluation of protein oscillations and an unexpected and relevant acceleration in the DNA repairing when suitable digital control matrix is implemented. Those effects suggest interesting perspectives for future scientific investigations. First of all, the proposed digital circuitry, receiving the p53 signal from a damaged cell, is able to repair the current level of genomic alteration. Moreover, the cell fate is newly conceived and bound by the modified pulsing mechanism of p53.
Ardito Marretta
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RM
Dipartimento di Ingegneria Strutturale e Geotecnica, Università di Palermo, Edificio 8, 90128, Palermo, Italy. romario@unipa.it
Barbaraci
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D000465:Algorithms; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology; D003198:Computer Simulation; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D018797:Cell Cycle Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2