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Purification of Ubiquitinated p53 Proteins from Mammalian Cells
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Purification of Ubiquitinated p53 Proteins from Mammalian Cells

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Dynamics of posttranslational modifications of p53

Qing-Duan Fan1, Guang Wu2, Zeng-Rong Liu3

  • 1Institute of Systems Biology, Shanghai University, 99 Shangda Road, Shanghai 200444, China ; College of Fundamental Studies, Shanghai University of Engineering Science, 333 Longteng Road, Shanghai 201620, China.

Computational and Mathematical Methods in Medicine
|June 6, 2014
PubMed

Insights

This study introduces a new model for cell apoptosis involving p53 with three states: unphosphorylated, phosphorylated, and acetylated. Simulations show acetylated p53 induces apoptosis, while phosphorylated p53 promotes DNA repair.

Area of Science:

  • Molecular Biology
  • Cellular Dynamics
  • Biophysics

Background:

  • Previous models of p53-mediated apoptosis focused on phosphorylation/dephosphorylation.
  • Experimental evidence suggests p53 acetylation at K164 and K120 induces apoptosis under DNA damage.

Purpose of the Study:

  • To propose a novel cell apoptosis network incorporating three p53 states: unphosphorylated, phosphorylated, and acetylated.
  • To investigate the dynamical insights of p53-induced cell apoptosis using time-delay differential equations.

Main Methods:

  • Formulation of a new cell apoptosis network based on existing models.
  • Development of time-delay differential equations (DDEs) to analyze the network dynamics.
  • Computational simulations to explore p53 states and their effects.

Main Results:

  • Simulations indicate gradual accumulation of acetylated p53, leading to Bax induction and apoptosis under sufficient DNA damage.
  • Phosphorylated p53 exhibits oscillatory behavior and initiates cellular repair mechanisms during DNA damage.
  • The model aligns with experimental observations regarding acetylated p53 accumulation.

Conclusions:

  • The three-state p53 model provides a more comprehensive understanding of cell apoptosis dynamics.
  • Acetylated p53 plays a critical role in initiating apoptosis, while phosphorylated p53 is involved in DNA repair.
  • This network model offers new dynamical insights into p53-regulated cellular fate decisions.

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