  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.
