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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Dual roles of SIRT1 in the BAX switch through the P53 module: A mathematical modeling study

Nan Liu1, Hongli Yang1, Liangui Yang1

  • 1School of Mathematical Sciences, Inner Mongolia University, Hohhot 010021, China.

Computational and Structural Biotechnology Journal
|December 1, 2021
PubMed

Insights

SIRT1 influences apoptosis by regulating the BAX switch. Both excess and deficiency of SIRT1 delay BAX opening and increase apoptosis thresholds, suggesting an optimal SIRT1 level for maximal apoptosis probability.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Systems Biology

Background:

  • SIRT1 is a deacetylase involved in stress response and regulates the tumor suppressor protein P53.
  • P53-dependent apoptosis is linked to the BCL-2 protein family, particularly BAX dynamics.
  • The precise role of SIRT1 in regulating BAX switching during apoptosis remains unclear.

Purpose of the Study:

  • To investigate the effect of SIRT1 on the BAX switch dynamics.
  • To elucidate the complex role of SIRT1 in apoptosis.
  • To determine the optimal concentration of SIRT1 for apoptosis induction.

Main Methods:

  • Construction of a small-scale protein network model.
  • Computer simulations to analyze SIRT1's impact on apoptosis pathways.
  • Analysis of BAX switch dynamics and apoptosis thresholds under varying SIRT1 levels.

Main Results:

  • SIRT1 excess or deficiency delays BAX switch opening and increases the apoptosis stimulus threshold.
  • An optimal concentration of SIRT1 was identified, maximizing apoptosis probability.
  • High SIRT1 concentrations, above optimal, are required for P53 oscillation.

Conclusions:

  • SIRT1 exhibits dual roles in promoting and inhibiting apoptosis, dependent on its concentration.
  • Optimal SIRT1 levels are crucial for efficient apoptosis induction.
  • Findings provide insights into SIRT1's role in cancer and stress response, with potential clinical implications.
Keywords:
ApoptosisBAX switchBifurcationP53-MDM2SIRT1

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