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学科主题基础医学
PDCD5 functions as a regulator of p53 dynamics in the DNA damage response
Zhuge, Changjing1; Sun, Xiaojuan2; Chen, Yingyu3; Lei, Jinzhi4
关键词PDCD5 P53 DNA damage Apoptosis Mathematical model
刊名JOURNAL OF THEORETICAL BIOLOGY
2016-01-07
DOI10.1016/j.jtbi.2015.09.025
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
WOS记录号WOS:000366791500001
项目编号BLX2014-29 ; 11272169 ; 91430101 ; 31370898
资助机构Fundamental Research Funds for the Central Universities ; National Natural Science Foundation of China
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64255
专题北京大学基础医学院_免疫学系
北京大学基础医学院
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
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GB/T 7714
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.
APA Zhuge, Changjing,Sun, Xiaojuan,Chen, Yingyu,&Lei, Jinzhi.(2016).PDCD5 functions as a regulator of p53 dynamics in the DNA damage response.JOURNAL OF THEORETICAL BIOLOGY,388(7),1-10.
MLA Zhuge, Changjing,et al."PDCD5 functions as a regulator of p53 dynamics in the DNA damage response".JOURNAL OF THEORETICAL BIOLOGY 388.7(2016):1-10.
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