Related Experiment Video
Updated: Jun 11, 2026
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Stress-specific response of the p53-Mdm2 feedback loop
Alexander Hunziker1, Mogens H Jensen, Sandeep Krishna
1Center for Models of Life, Niels Bohr Institute, Copenhagen, Denmark.
BMC Systems Biology
|July 14, 2010
Summary
A mathematical model of the p53-Mdm2 feedback loop shows how this system generates diverse responses to different cellular stresses. This flexibility allows the p53 pathway to adapt to various conditions.
Area of Science:
- Cellular Biology
- Systems Biology
- Mathematical Modeling
Background:
- The p53 signaling pathway regulates critical cellular processes like senescence, cell-cycle arrest, and apoptosis in response to various stresses.
- All stress signals converge on the transcription factor p53, yet the pathway exhibits stress-specific downstream gene expression patterns.
Purpose of the Study:
- To investigate the mechanisms underlying the p53 pathway's flexible, stress-specific responses.
- To model the core negative feedback loop involving p53 and its inhibitor, Mdm2.
Main Methods:
- Construction of a mathematical model of the p53-Mdm2 negative feedback loop.
- Simulation of the model under different stress conditions (e.g., DNA damage, hypoxia).
Main Results:
- The model accurately reproduces diverse output behaviors, including steady states (low/high p53 and Mdm2) and oscillatory patterns (spiky oscillations with varying average p53 levels).
- These varied outputs correspond to different cellular stress inputs.
Conclusions:
- A simple negative feedback loop can generate the observed flexibility in the p53 system's stress response.
- The model serves as a predictive framework for understanding p53 responses to different stresses and genetic variations.
Related Concept Videos
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:36DNA Damage can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
02:36DNA Damage Can Stall the Cell Cycle
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...