PDCD5 interacts with p53 and functions as a regulator of p53 dynamics in the 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.
Keywords
Cite
@article{arxiv.1503.08274,
title = {PDCD5 interacts with p53 and functions as a regulator of p53 dynamics in the DNA damage response},
author = {Changjing Zhuge and Xiaojuan Sun and Yingyu Chen and Jinzhi Lei},
journal= {arXiv preprint arXiv:1503.08274},
year = {2015}
}
Comments
12 pages, 7 figures