title: PDCD5 functions as a regulator of p53 dynamics in the DNA damage response.
abstract: 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.
authors.affiliation: College of Sciences, Beijing Forestry University, 35 Tsinghua East Road, Beijing 100083, China.
authors.forename: Changjing
authors.initials: C
authors.lastname: Zhuge
authors.affiliation: School of Science, Beijing University of Posts and Telecommunications, 10 Xitucheng Road, Beijing 100876, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Laboratory of Medical Immunology, School of Basic Medical Science, Peking University, 38 Xueyuan Road, Beijing 100083, China.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Bioinformatics, Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University, Beijing 100084, China. Electronic address: jzlei@tsinghua.edu.cn.
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Lei
mesh_terms: D000465:Algorithms; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Apoptosis; DNA damage; Mathematical model; P53; PDCD5