基于混合功能Petri网的p53转录活性的模拟验证

Simulation-based validation of the p53 transcriptional activity with hybrid functional petri net.

作者信息

Doi Atsushi, Nagasaki Masao, Matsuno Hiroshi, Miyano Satoru

机构信息

Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

出版信息

In Silico Biol. 2006;6(1-2):1-13.

PMID:16789909

Abstract

MDM2 and p19ARF are essential proteins in cancer pathways forming a complex with protein p53 to control the transcriptional activity of protein p53. It is confirmed that protein p53 loses its transcriptional activity by forming the functional dimer with protein MDM2. However, it is still unclear that protein p53 keeps its transcriptional activity when it forms the trimer with proteins MDM2 and p19ARF. We have observed mutual behaviors among genes p53, MDM2, p19ARF and their products on a computational model with hybrid functional Petri net (HFPN) which is constructed based on information described in the literature. The simulation results suggested that protein p53 should have the transcriptional activity in the forms of the trimer of proteins p53, MDM2, and p19ARE This paper also discusses the advantages of HFPN based modeling method in terms of pathway description for simulations.

摘要

MDM2和p19ARF是癌症通路中的关键蛋白，它们与蛋白p53形成复合物以控制蛋白p53的转录活性。已证实蛋白p53通过与蛋白MDM2形成功能性二聚体而失去其转录活性。然而，当蛋白p53与蛋白MDM2和p19ARF形成三聚体时，其是否仍保持转录活性尚不清楚。我们基于文献中描述的信息，利用混合功能Petri网（HFPN）构建了一个计算模型，观察了基因p53、MDM2、p19ARF及其产物之间的相互作用。模拟结果表明，蛋白p53以p53、MDM2和p19ARF蛋白三聚体的形式应具有转录活性。本文还讨论了基于HFPN的建模方法在模拟通路描述方面的优势。