Numerical and Experimental Analysis of the p53-mdm2 Regulatory Pathway

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.