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Updated: May 5, 2026
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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
Published on: September 28, 2012
13.8K
Coordination between p21 and DDB2 in the cellular response to UV radiation
Hao Li1, Xiao-Peng Zhang, Feng Liu
1National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing, China.
Plos One
|November 22, 2013
Summary
The p53 network
Area of Science:
- Molecular Biology
- Cell Biology
- Systems Biology
Background:
- The tumor suppressor p53 is crucial for cellular responses to DNA damage.
- p53 regulates target genes, including p21 (cell cycle arrest, apoptosis inhibition) and DDB2 (damaged-DNA binding protein 2, apoptosis promotion).
- DDB2 mediates p21 degradation post-UV DNA damage, influencing cell fate.
Purpose of the Study:
- To develop an integrated model of the p53 network.
- To explore UV-irradiated cell decision-making between survival and death.
- To elucidate the modulation of p21 and DDB2 activities.
Main Methods:
- Development of an integrated computational model of the p53 signaling network.
- Numerical simulations to analyze network dynamics under varying DNA damage levels.
- Investigation of p53 concentration-dependent promoter selectivity and gene expression patterns.
Main Results:
- p53 activation is progressive, with concentration-dependent promoter selectivity.
- Minor DNA damage leads to intermediate p53 levels, p21 induction, cell cycle arrest, and DNA repair.
- Severe DNA damage induces a two-phase p53 response, high p53 levels, p21 degradation by DDB2, E2F1 activation, and apoptosis.
- PTEN amplifies p53 activation, promoting apoptosis.
Conclusions:
- p21 downregulation is essential for apoptosis induction following DNA damage.
- The p53 network dynamics, regulated by feedback and feed-forward loops, dictate cell fate decisions.
- Fine-tuning of p21 regulation is critical for the DNA damage response.
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