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Dynamics of p53 is known to play important roles in the regulation of cellfate decisions in response to various stresses, and PDCD5 functions as aco-activator of p53 to modulate the p53 dynamics. In the present paper, weinvestigate how p53 dynamics are modulated by PDCD5 during the DNA damageresponse using methods of bifurcation analysis and potential landscape. Ourresults reveal that p53 activities can display rich dynamics under differentPDCD5 levels, including monostability, bistability with two stable steadystates, oscillations, and co-existence of a stable steady state and anoscillatory state. Physical properties of the p53 oscillations are furthershown by the potential landscape, in which the potential force attracts thesystem state to the limit cycle attractor, and the curl flux force drives thecoherent oscillation along the cyclic. We also investigate the effect of PDCD5efficiency on inducing the p53 oscillations. We show that Hopf bifurcation isinduced by increasing the PDCD5 efficiency, and the system dynamics show cleartransition features in both barrier height and energy dissipation when theefficiency is close to the bifurcation point. This study provides a globalpicture of how PDCD5 regulates p53 dynamics via the interaction with thep53-Mdm2 oscillator and can be helpful in understanding the complicate p53dynamics in a more complete p53 pathway.

Bifurcation analysis and potential landscape of the p53-Mdm2 oscillator regulated by the co-activator PDCD5