Noise Response of P53 Oscillation against System Size Scaling

Abstract

p53 is a DNA binding protein regulating the expression of various other proteins under DNA damaging cell stress. Based on different type and extent of DNA damage, p53 up-regulates different sets of proteins and triggers cell cycle arrest, DNA repair or Apoptosis. Given the importance of p53 regarding to its role in cell fate decision, it is only reasonable for such molecules to be under delicate regulation.One interesting observation on p53 dynamics is that when stress signal is activated, rather than staying in an activated higher level, the concentration of p53 pulses with a period of around 5.5 hours, in a rather noisy manner. mdm2, one of p53's main regulators, goes through a similar pulsing process, with a same period as the oscillation of p53 and a stable delay in phase. So far, different theories on both the origin of p53 oscillation and its variation on amplitude are explored. Yet the relation between the size of the system and the noise-driven oscillation, or rather, whether the oscillation is robust against the size variation is hardly mentioned. Given that the absolute number of molecules in a single cell being difficult to assess experimentally, along with the fact that cell size varies for different cell type in a single species, we believe a discussion on how such dynamics behaves under cell size variation being valid for both theoretical and application purposes. In our work, we adopted and modified an existing model. Based on it, we shall discuss its noise driven oscillation behaviour and explore its response against system size variation both numerically and analytically.