Dynamics of p53 and Wnt cross talk

TL;DR

This paper investigates the interaction between p53 and Wnt signaling networks, revealing how variations in key molecules can switch cellular states and potentially prevent apoptosis through coupled dynamics analysis.

Contribution

It introduces a coupled p53-Wnt model and explores how molecular variations influence oscillatory states and cell fate decisions.

Findings

Variation in Nutlin affects oscillation states and cycle arrest.

Axin concentration modulates p53 dynamics.

Altered interaction rates can prevent apoptosis.

Abstract

We present the mechanism of interaction of Wnt network module, which is responsible for periodic sometogenesis, with p53 regulatory network, which is one of the main regulators of various cellular functions, and switching of various oscillating states by investigating p53-Wnt model. The variation in Nutlin concentration in p53 regulating network drives the Wnt network module to different states, stabilized, damped and sustain oscillation states, and even to cycle arrest. Similarly, the change in Axin concentration in Wnt could able to modulate the p53 dynamics at these states. We then solve the set of coupled ordinary differential equations of the model using quasi steady state approximation. We, further, demonstrate the change of p53 and Gsk3 interaction rate, due to hypothetical catalytic reaction or external stimuli, can able to regulate the dynamics of the two network modules, and even can control their dynamics to protect the system from cycle arrest (apoptosis).