title: Bifurcation analysis and potential landscapes of the p53-Mdm2 module regulated by the co-activator programmed cell death 5.
abstract: The dynamics of p53 play important roles in the regulation of cell fate decisions in response to various stresses, and programmed cell death 5 (PDCD5) functions as a co-activator of p53 that modulates p53 dynamics. In the present paper, we investigated how p53 dynamics are modulated by PDCD5 during the deoxyribose nucleic acid damage response using methods of bifurcation analysis and potential landscape. Our results revealed that p53 activities display rich dynamics under different PDCD5 levels, including monostability, bistability with two stable steady states, oscillations, and the coexistence of a stable steady state (or two states) and an oscillatory state. The physical properties of the p53 oscillations were further demonstrated by the potential landscape in which the potential force attracts the system state to the limit cycle attractor, and the curl flux force drives coherent oscillation along the cyclic trajectory. We also investigated the efficiency with which PDCD5 induced p53 oscillations. We show that Hopf bifurcation can be induced by increasing the PDCD5 efficiency and that the system dynamics exhibited clear transition features in both barrier height and energy dissipation when the efficiency was close to the bifurcation point.
authors.affiliation: School of Mathematics and Systems Science and LMIB, Beihang University, Beijing 100191, China and School of Statistics and Mathematics, Inner Mongolia University of Finance and Economics, Hohhot 010070, China.
authors.forename: Yuanhong
authors.initials: Y
authors.lastname: Bi
authors.affiliation: School of Mathematics and Systems Science and LMIB, Beihang University, Beijing 100191, China.
authors.forename: Zhuoqin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: College of Sciences, Beijing Forestry University, Beijing 100083, China.
authors.forename: Changjing
authors.initials: C
authors.lastname: Zhuge
authors.affiliation: MOE Key Laboratory of Bioinformatics, Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University, Beijing 100084, China.
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Lei
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D008954:Models, Biological; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016159:Tumor Suppressor Protein p53; D051736:Proto-Oncogene Proteins c-mdm2