Stochastic modeling of p53-regulated apoptosis upon radiation damage

TL;DR

This paper presents a stochastic model of radiation-induced apoptosis focusing on p53 pathways, identifying key proteins and proposing targeted mitigation strategies based on simulation results.

Contribution

It introduces a novel stochastic model of p53-regulated apoptosis that reproduces experimental oscillations and suggests specific protein inhibition strategies for radiation damage mitigation.

Findings

Inhibition of PUMA is effective if applied immediately after radiation.

Inhibition of tBid is more effective at later stages.

The model reproduces known p53 oscillations.

Abstract

We develop and study the evolution of a model of radiation induced apoptosis in cells using stochastic simulations, and identified key protein targets for effective mitigation of radiation damage. We identified several key proteins associated with cellular apoptosis using an extensive literature survey. In particular, we focus on the p53 transcription dependent and p53 transcription independent pathways for mitochondrial apoptosis. Our model reproduces known p53 oscillations following radiation damage. The key, experimentally testable hypotheses that we generate are - inhibition of PUMA is an effective strategy for mitigation of radiation damage if the treatment is administered immediately, at later stages following radiation damage, inhibition of tBid is more effective.