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学科主题: 基础医学
题名:
PDCD5-Regulated Cell Fate Decision after Ultraviolet-Irradiation-Induced DNA Damage
作者: Zhuge, Changjing1; Chang, Ying2; Li, Yanjun2; Chen, Yingyu2; Lei, Jinzhi1
刊名: BIOPHYSICAL JOURNAL
发表日期: 2011-12-07
DOI: 10.1016/j.bpj.2011.10.044
卷: 101, 期:11, 页:2582-2591
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biophysics
研究领域[WOS]: Biophysics
关键词[WOS]: HUMAN PDCD5 PROTEIN ; P53 PULSES ; P53-INDUCED APOPTOSIS ; TUMOR-CELLS ; DEATH 5 ; GENE ; EXPRESSION ; REPAIR ; MODEL ; BISTABILITY
英文摘要:

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.

语种: 英语
所属项目编号: 2011CB910103 ; 30871263 ; 10971113
项目资助者: National Key Project for Basic Research of China (973) ; National Natural Science Foundation of China
WOS记录号: WOS:000297897300007
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/65302
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.Tsinghua Univ, Zhou Pei Yuan Ctr Appl Math, Beijing 100084, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Lab Med Immunol, Beijing 100871, Peoples R China

Recommended Citation:
Zhuge, Changjing,Chang, Ying,Li, Yanjun,et al. PDCD5-Regulated Cell Fate Decision after Ultraviolet-Irradiation-Induced DNA Damage[J]. BIOPHYSICAL JOURNAL,2011,101(11):2582-2591.
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