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

Published on: August 4, 2019

Crosstalk between p53 and nuclear factor-B systems: pro- and anti-apoptotic functions of NF-B

K Puszynski1, R Bertolusso, T Lipniacki

  • 1Silesian University of Technology, Institute of Automatic Control, Gliwice, Poland.

IET Systems Biology
|October 30, 2010
PubMed

Insights

Nuclear factor kappa B (NF-B) and p53 pathways interact dynamically, influencing cell death. The timing of NF-B and p53 activation determines whether cells survive or undergo apoptosis, impacting cancer development.

Area of Science:

  • Molecular Biology
  • Systems Biology
  • Immunology

Background:

  • Nuclear factors p53 and NF-B regulate critical cellular processes like apoptosis and immune responses.
  • Existing research indicates complex interactions, including cooperation and antagonism, between p53 and NF-B pathways.
  • Understanding these crosstalks is crucial for deciphering cellular fate decisions.

Purpose of the Study:

  • To develop and analyze a theoretical model of the p53-NF-B network with bidirectional signaling.
  • To investigate the consequences of NF-B upregulating p53 and p53 attenuating NF-B inhibitors (IB and A20).
  • To explore the context-dependent roles of NF-B in apoptosis based on pathway activation timing.

Main Methods:

  • Construction of a theoretical crosstalk model integrating existing p53 and NF-B pathway models.
  • Simulation of cellular responses to stimuli like tumor necrosis factor (TNF) and gamma irradiation.
  • Analysis of the dynamic interplay between p53 and NF-B activation under different stimulation protocols.

Main Results:

  • The model demonstrates that NF-B can exert both anti-apoptotic and pro-apoptotic effects.
  • TNF stimulation before irradiation confers resistance to apoptosis, while TNF after irradiation enhances apoptosis.
  • The sequence and timing of p53 and NF-B pathway activation significantly alter cellular outcomes.

Conclusions:

  • The dynamical context of p53 and NF-B pathway activation dictates NF-B's role in apoptosis.
  • These findings offer insights into the multifaceted roles of NF-B in cancer and immune responses.
  • The study highlights the importance of systems-level analysis for understanding complex biological networks.

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