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

DOI10.1016/J.JTBI.2015.09.025zbMATH Open1343.92182arXiv1503.08274OpenAlexW1803836217WikidataQ38830572 ScholiaQ38830572MaRDI QIDQ304652FDOQ304652

Authors: Changjing Zhuge, Xiaojuan Sun, Yingyu Chen, Jinzhi Lei 

Publication date: 26 August 2016

Published in: Journal of Theoretical Biology (Search for Journal in Brave)

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.

Full work available at URL: https://arxiv.org/abs/1503.08274

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zbMATH Keywords

apoptosisDNA damageP53PDCD5pulsed oscillations

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.) (92C45)

Cited In (7)

• Bifurcation analysis and potential landscapes of the p53-mdm2 module regulated by the co-activator programmed cell death 5
• Stability and bifurcation analyses of p53 gene regulatory network with time delay
• Interplay of p53 and XIAP protein dynamics orchestrates cell fate in response to chemotherapy
• Modeling the roles of 14-3-3 σ and Wip1 in p53 dynamics and programmed cell death*
• Multiple Time Delays Induced Dynamics of p53 Gene Regulatory Network
• Bifurcation and Potential Landscape of p53 Dynamics Depending on PDCD5 Level and ATM Degradation Rate
• Mathematical modelling of core regulatory mechanism in p53 protein that activates apoptotic switch

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