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癌细胞的数字控制电路及其凋亡

Digital control circuitry of cancer cell and its apoptosis.

作者信息

Ardito Marretta R M, Barbaraci G

机构信息

Dipartimento di Ingegneria Strutturale e Geotecnica, Università di Palermo, Edificio 8, 90128, Palermo, Italy.

出版信息

Mol Cell Biomech. 2009 Sep;6(3):175-89.

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 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.

摘要

本研究通过一个典型的航空航天系统架构,提出了一种人类癌细胞电路的工程设计,其中分配了一个数字最优控制矩阵来修复DNA损伤水平和/或触发其凋亡。在此,所设想的机制是在考虑癌症研究现状的基础上提出的。然而,它可以进一步推广。关于癌症病理学的最新研究表明肿瘤抑制蛋白p53及其拮抗剂癌基因Mdm2起着主要作用。实验和理论方法一致推断出当基因组完整性受损时p53的“数字”反应。一旦存在DNA损伤,p53及其拮抗剂癌基因Mdm2的相互影响就会形成一个反馈回路。在这项工作中,从这些当前结果出发,基于数字最优控制定律提出了一种新的分子机制,据此p53和Mdm2蛋白的活性可以由适当的电路表示,并由数字系统的最优控制定律控制。当实施合适的数字控制矩阵时,该过程可获得蛋白质振荡的实时序列评估以及DNA修复中意外且相关的加速。这些效应为未来的科学研究提供了有趣的视角。首先,所提出的数字电路从受损细胞接收p53信号,能够修复当前的基因组改变水平。此外,细胞命运由p53的修饰脉冲机制重新构想并受其约束。

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