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学科主题: 基础医学
题名:
PDCD5 functions as a regulator of p53 dynamics in the DNA damage response
作者: Zhuge, Changjing1; Sun, Xiaojuan2; Chen, Yingyu3; Lei, Jinzhi4
关键词: PDCD5 ; P53 ; DNA damage ; Apoptosis ; Mathematical model
刊名: JOURNAL OF THEORETICAL BIOLOGY
发表日期: 2016-01-07
DOI: 10.1016/j.jtbi.2015.09.025
卷: 388, 期:7, 页:1-10
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biology ; Mathematical & Computational Biology
研究领域[WOS]: Life Sciences & Biomedicine - Other Topics ; Mathematical & Computational Biology
关键词[WOS]: CELL-DEATH 5 ; FATE DECISION ; P53-DEPENDENT APOPTOSIS ; PROGNOSTIC-SIGNIFICANCE ; REDUCED EXPRESSION ; TUMOR-CELLS ; PROTEIN ; GENE ; MDM2 ; ATM
英文摘要:

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. (C) 2015 Elsevier Ltd. All rights reserved.

语种: 英语
所属项目编号: BLX2014-29 ; 11272169 ; 91430101 ; 31370898
项目资助者: Fundamental Research Funds for the Central Universities ; National Natural Science Foundation of China
WOS记录号: WOS:000366791500001
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64255
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Beijing Forestry Univ, Coll Sci, Beijing 100083, Peoples R China
2.Beijing Univ Posts & Telecommun, Sch Sci, Beijing 100876, Peoples R China
3.Peking Univ, Sch Basic Med Sci, Lab Med Immunol, Beijing 100083, Peoples R China
4.Tsinghua Univ, Zhou Pei Yuan Ctr Appl Math, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China

Recommended Citation:
Zhuge, Changjing,Sun, Xiaojuan,Chen, Yingyu,et al. PDCD5 functions as a regulator of p53 dynamics in the DNA damage response[J]. JOURNAL OF THEORETICAL BIOLOGY,2016,388(7):1-10.
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