title: The dynamics of p53 in single cells: physiologically based ODE and reaction-diffusion PDE models.
abstract: The intracellular signalling network of the p53 protein plays important roles in genome protection and the control of cell cycle phase transitions. Recently observed oscillatory behaviour in single cells under stress conditions has inspired several research groups to simulate and study the dynamics of the protein with the aim of gaining a proper understanding of the physiological meanings of the oscillations. We propose compartmental ODE and PDE models of p53 activation and regulation in single cells following DNA damage and we show that the p53 oscillations can be retrieved by plainly involving p53-Mdm2 and ATM-p53-Wip1 negative feedbacks, which are sufficient for oscillations experimentally, with no further need to introduce any delays into the protein responses and without considering additional positive feedback.
authors: UPMC, Laboratoire Jacques-Louis Lions, 4 Place Jussieu, F-75005 Paris, France & INRIA Paris-Rocquencourt, MAMBA project-team, Paris and Rocquencourt, France.
authors: Ján
authors: J
authors: Eliaš
authors: Luna
authors: L
authors: Dimitrio
authors: Jean
authors: J
authors: Clairambault
authors: Roberto
authors: R
authors: Natalini
mesh_terms: D000818:Animals; D002453:Cell Cycle; D004249:DNA Damage; D004058:Diffusion; D006801:Humans; D008954:Models, Biological; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2; C000607458:PPM1D protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C