A plausible model for bimodal p53 switch in DNA damage response

Tingzhe Sun; Jun Cui

doi:10.1016/j.febslet.2014.01.044

A plausible model for bimodal p53 switch in DNA damage response

FEBS Lett. 2014 Mar 3;588(5):815-21. doi: 10.1016/j.febslet.2014.01.044. Epub 2014 Jan 31.

Authors

Tingzhe Sun¹, Jun Cui²

Affiliations

¹ School of Life Sciences, AnQing Normal University, AnQing 246011, Anhui, PR China. Electronic address: [email protected].
² 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: [email protected].

PMID: 24486906
DOI: 10.1016/j.febslet.2014.01.044

Abstract

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.

Keywords: Bimodal switch; Cell fate decision; Feedback loop; Monotonic increasing; p53 Pulse.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Algorithms
Computer Simulation
DNA Damage*
DNA Repair
Feedback, Physiological
Gene Expression Regulation
Humans
Models, Biological*
Protein Stability
Proto-Oncogene Proteins c-mdm2 / physiology
Tumor Suppressor Protein p53 / physiology*

Substances

TP53 protein, human
Tumor Suppressor Protein p53
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2