The p53-MDM2 network: from oscillations to apoptosis

TL;DR

This paper reviews the p53-MDM2 regulatory network, highlighting its oscillatory behavior and role in apoptosis, from a systems biology perspective, and proposes testable predictions about cell cycle arrest and cell death.

Contribution

It provides a systems biology analysis of the p53-MDM2 network, emphasizing its oscillations and regulatory role in stress responses and apoptosis, with new testable predictions.

Findings

Predicted oscillatory dynamics of p53-MDM2 under stress

Identified key regulatory points influencing cell fate

Proposed experimental tests for network behavior

Abstract

The p53 protein is well-known for its tumour suppressor function. The p53-MDM2 negative feedback loop constitutes the core module of a network of regulatory interactions activated under cellular stress. In normal cells, the level of p53 proteins is kept low by MDM2, i.e. MDM2 negatively regulates the activity of p53. In the case of DNA damage,the p53-mediated pathways are activated leading to cell cycle arrest and repair of the DNA. If repair is not possible due to excessive damage, the p53-mediated apoptotic pathway is activated bringing about cell death. In this paper, we give an overview of our studies on the p53-MDM2 module and the associated pathways from a systems biology perspective. We discuss a number of key predictions, related to some specific aspects of cell cycle arrest and cell death, which could be tested in experiments.