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

J Theor Biol 2016 Jan 9;388:1-10. Epub 2015 Oct 9.

MOE Key Laboratory of Bioinformatics, Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University, Beijing 100084, China. Electronic address:

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.

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http://dx.doi.org/10.1016/j.jtbi.2015.09.025DOI Listing
January 2016
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