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

The tumor suppressor p53 plays a central role in cell fate decisions after DNA damage. Programmed Cell Death 5 (PDCD5) interacts with the p53 pathway to promote cell apoptosis. Recombinant human PDCD5 can significantly sensitize different cancers to chemotherapies. In the present paper, we construct...

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Bibliographic Details
Published in:Journal of theoretical biology 2016-01, Vol.388, p.1-10
Main Authors: Zhuge, Changjing, Sun, Xiaojuan, Chen, Yingyu, Lei, Jinzhi
Format: Article
Language:English
Subjects:
Algorithms
Apoptosis
Apoptosis - physiology
Apoptosis Regulatory Proteins - metabolism
Cell Line, Tumor
Computer Simulation
DNA Damage
DNA Repair
Humans
Mathematical model
Models, Biological
Neoplasm Proteins - metabolism
P53
PDCD5
Protein Binding
Signal Transduction
Tumor Suppressor Protein p53 - metabolism
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Summary:The tumor suppressor p53 plays a central role in cell fate decisions after DNA damage. Programmed Cell Death 5 (PDCD5) interacts 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 and regulates p53-dependent cell fate decisions via the mediation of p53 dynamics. The effects of PDCD5 are dose-dependent, such that p53 activity exhibits sustained low level, pulsed oscillations, or sustained high level dynamics depending on the PDCD5 level following DNA damage. 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. •The effects of PDCD5 on p53-mediated cell fate decisions during the DNA damage response are studied.•PDCD5 regulates p53-dependent cell fate decisions via the mediation of p53 dynamics.•The effects of PDCD5 are dose-dependent.•PDCD5 regulates caspase-3 activation via two mechanisms during the two phases of p53 dynamics.
ISSN:0022-5193
1095-8541
DOI:10.1016/j.jtbi.2015.09.025