title: PDCD5-regulated cell fate decision after ultraviolet-irradiation-induced DNA damage.
abstract: Programmed cell death 5 (PDCD5) is a human apoptosis-related molecule that is involved in both the cytoplasmic caspase-3 activity pathway (by regulating Bax translocation from cytoplasm to mitochondria) and the nuclear pathway (by interacting with Tip60). In this study, we developed a mathematical model of the PDCD5-regulated switching of the cell response from DNA repair to apoptosis after ultraviolet irradiation-induced DNA damage. We established the model by combining several hypotheses with experimental observations. Our simulations indicate that the ultimate cell response to DNA damage is dependent on a signal threshold mechanism, and the PDCD5 promotion of Bax translocation plays an essential role in PDCD5-regulated cell apoptosis. Furthermore, the model simulations revealed that PDCD5 nuclear translocation can attenuate cell apoptosis, and PDCD5 interactions with Tip60 can accelerate DNA damage-induced apoptosis, but the final cell fate decision is insensitive to the PDCD5-Tip60 interaction. These results are consistent with experimental observations. The effect of recombinant human PDCD5 was also investigated and shown to sensitize cells to DNA damage by promoting caspase-3 activity.
authors.affiliation: Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University, Beijing, China.
authors.forename: Changjing
authors.initials: C
authors.lastname: Zhuge
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Li
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Lei
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D019070:Cell Lineage / Q000528:radiation effects*; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D003198:Computer Simulation; D004249:DNA Damage; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000528:radiation effects; D021381:Protein Transport / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D051028:bcl-2-Associated X Protein; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; D053148:Caspase 3