Fluctuations in network dynamics: SMAR1 can trigger apoptosis

TL;DR

This paper investigates how fluctuations in SMAR1 influence p53 network dynamics, showing that SMAR1 can induce apoptosis through amplitude death, and explores regulatory mechanisms to prevent cell death.

Contribution

It reveals the role of SMAR1 fluctuations in triggering apoptosis and proposes regulatory strategies involving p300 and HDAC1 to prevent this process.

Findings

SMAR1 fluctuations can induce amplitude death in p53 network.

Permutation entropy distinguishes normal and apoptotic states.

Regulation of SMAR1 with p300 and HDAC1 can prevent apoptosis.

Abstract

SMAR1 is a sensitive signaling molecule in p53 regulatory network which can drive p53 network dynamics to three distinct states, namely, stabilized (two), damped and sustain oscillation states. In the interaction of p53 network with SMAR1, p53 network sees SMAR1 as a sub-network with its new complexes formed by SMAR1, where SMAR1 is the central node, and fluctuations in SMAR1 concentration is propagated as a stress signal throughout the network. Excess stress induced by SMAR1 can drive p53 network dynamics to amplitude death scenario which corresponds to apoptotic state. The permutation entropy calculated for normal state is minimum indicating self-organized behavior, whereas for apoptotic state, the value is maximum showing breakdown of self-organization. We also show that the regulation of SMAR1 togather with other signaling molecules p300 and HDAC1 in the p53 regulatory network can be engineered to extend the range of stress such that the system can be save from apoptosis.