Time delay as a key to Apoptosis Induction in the p53 Network

TL;DR

This paper explores how the timing of protein interactions in the p53 network influences apoptosis, revealing that a decrease in dissociation constant triggers cell death more accurately than an increase, with implications for cancer understanding.

Contribution

It introduces a minimal dynamic model showing that apoptosis induction depends on the dissociation constant variation, emphasizing the importance of timing in the p53-mdm2 feedback loop.

Findings

Decreased dissociation constant k better explains experimental data.

The response mechanism is robust to parameter changes.

Weak points in the system may relate to cancer onset.

Abstract

A feedback mechanism that involves the proteins p53 and mdm2, induces cell death as a controled response to severe DNA damage. A minimal model for this mechanism demonstrates that the respone may be dynamic and connected with the time needed to translate the mdm2 protein. The response takes place if the dissociation constant k between p53 and mdm2 varies from its normal value. Although it is widely believed that it is an increase in k that triggers the response, we show that the experimental behaviour is better described by a decrease in the dissociation constant. The response is quite robust upon changes in the parameters of the system, as required by any control mechanism, except for few weak points, which could be connected with the onset of cancer.