A plausible model for bimodal p53 switch in DNA damage response.
p53 is a tumor suppressor and the p53 dynamics displays stimulus dependent patterns. Recent evidence suggests a bimodal p53 switch in cell fate decision. However, no theoretical studies have been proposed to investigate bimodal p53 induction. Here we constructed a model and showed that MDM2-p53 mRNA binding might contribute to bimodal p53 switch through an intrinsic positive feedback loop. Lower damage favored pulsing while monotonic increasing was generated with higher damage. Bimodal p53 dynamics was largely influenced by cellular MDM2 and elevated p53/MDM2 ratios with increasing etoposide favor mono-ubiquitination. Our model replicated recent experiments and provided potential insights into dynamic mechanisms of bimodal switch.
School of Life Sciences, AnQing Normal University, AnQing 246011, Anhui, PR China. Electronic address: confucian007@126.com.
Tingzhe
T
Sun
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, Guangdong, PR China. Electronic address: cuij5@mail.sysu.edu.cn.
Jun
J
Cui
D000465:Algorithms; D003198:Computer Simulation; D004249:DNA Damage; D004260:DNA Repair; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
Bimodal switch; Cell fate decision; Feedback loop; Monotonic increasing; p53 Pulse