Research Article
Numerical and Experimental Analysis of the p53-mdm2 Regulatory Pathway
@INPROCEEDINGS{10.1007/978-3-642-14859-0_20, author={Ingeborg Leeuwen and Ian Sanders and Oliver Staples and Sonia Lain and Alastair Munro}, title={Numerical and Experimental Analysis of the p53-mdm2 Regulatory Pathway}, proceedings={Digital Ecosystems. Third International Conference, OPAALS 2010, Aracuju, Sergipe, Brazil, March 22-23, 2010, Revised Selected Papers}, proceedings_a={OPAALS}, year={2012}, month={5}, keywords={Mathematical modelling Systems Biology Oscillations Pulses Cell Cycle Cancer}, doi={10.1007/978-3-642-14859-0_20} }- Ingeborg Leeuwen
Ian Sanders
Oliver Staples
Sonia Lain
Alastair Munro
Year: 2012
Numerical and Experimental Analysis of the p53-mdm2 Regulatory Pathway
OPAALS
Springer
DOI: 10.1007/978-3-642-14859-0_20
Abstract
The p53 tumour suppressor plays key regulatory roles in various fundamental biological processes, including development, ageing and cell differentiation. It is therefore known as “the guardian of the genome” and is currently the most extensively studied protein worldwide. Besides members of the biomedical community, who view p53 as a promising target for novel anti-cancer therapies, the complex network of protein interactions modulating p53’s activity has captivated the attention of theoreticians and modellers due to the possible occurrence of oscillations in protein levels in response to stress. This paper presents new insights into the behaviour of the p53 network, which we acquired by combining mathematical and experimental techniques. Notably, our data raises the question of whether the discrete p53 pulses in single cells, observed using fluorescent labelling, could in fact be an artefact. Furthermore, we propose a new model for the p53 pathway that is amenable to analysis by computational methods developed within the OPAALS project.