PDCD5 interacts with p53 and functions as a regulator of p53 dynamics in the DNA damage response

TL;DR

This study uses a computational model to explore how PDCD5 influences p53 dynamics and cell fate decisions during DNA damage response, revealing dose-dependent effects on p53 behavior and apoptosis regulation.

Contribution

The paper introduces a novel computational model incorporating PDCD5 interactions in the p53 pathway, elucidating its regulatory role in p53 dynamics and cell fate decisions.

Findings

PDCD5 acts as a co-activator of p53.

PDCD5 influences p53 dynamics in a dose-dependent manner.

PDCD5 regulates caspase-3 activation during DNA damage response.

Abstract

The tumor suppressor p53 plays a central role in cell fate decisions after DNA damage. Programmed Cell Death 5 (PDCD5) is known to interact with the p53 pathway to promote cell apoptosis. Recombinant human PDCD5 can significantly sensitize different cancers to chemotherapies. In the present paper, we construct a computational model that includes PDCD5 interactions in the p53 signaling network and study the effects of PDCD5 on p53-mediated cell fate decisions during the DNA damage response. Our results revealed that PDCD5 functions as a co-activator of p53 that regulates p53-dependent cell fate decisions via the mediation of p53 dynamics. The effects of PDCD5 are dose-dependent such that p53 can display either sustained or pulsed dynamics at different PDCD5 levels. Moreover, PDCD5 regulates caspase-3 activation via two mechanisms during the two phases of sustained and pulsed p53 dynamics. This study provides insights regarding how PDCD5 functions as a regulator of the p53 pathway and might be helpful for increasing our understanding of the molecular mechanisms by which PDCD5 can be used to treat cancers.