Oscillations of the p53-Akt Network and Their Impact on Cell Survival and Death
Author Information
Author(s): Wee Keng Boon, Surana Uttam, Aguda Baltazar D.
Primary Institution: Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research), Singapore
Hypothesis
The physiological significance of the experimentally observed oscillations could be found in their role in regulating the switching behavior of the p53-AKT network between pro-survival and pro-apoptotic states.
Conclusion
The p53-AKT network exhibits sustained oscillations that influence cell fate decisions between survival and apoptosis.
Supporting Evidence
- Oscillations in p53 protein levels induce higher expression of p53-target genes compared to non-oscillatory p53.
- The model predicts that oscillation periods of p53 are between 3.5 to 5.2 hours.
- Cells exposed to higher radiation intensities show increased oscillation frequencies of p53.
- Early-switching points in the model indicate that lower radiation doses can trigger significant cellular responses.
Takeaway
This study shows that the p53 protein can switch between helping cells survive and causing them to die, depending on how it oscillates in response to DNA damage.
Methodology
The study used a mathematical model to simulate the dynamics of the p53-AKT network and its oscillations in response to ionizing radiation.
Limitations
The model's predictions may not fully capture the complexity of biological systems and the variability in cellular responses.
Digital Object Identifier (DOI)
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