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学科主题基础医学
The HDAC inhibitor depsipeptide transactivates the p53/p21 pathway by inducing DNA damage
Wang, Haiying1; Zhou, Wen1; Zheng, Zhixing1; Zhang, Ping1; Tu, Bo1; He, Qihua2,3; Zhu, Wei-Guo1
关键词Depsipeptide DNA damage ROS p53
刊名DNA REPAIR
2012-02-01
DOI10.1016/j.dnarep.2011.10.014
11期:2页:146-156
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Genetics & Heredity ; Toxicology
研究领域[WOS]Genetics & Heredity ; Toxicology
关键词[WOS]HISTONE DEACETYLASE INHIBITORS ; PHOSPHORYLATION-ACETYLATION CASCADE ; LUNG-CANCER CELLS ; HUMAN P53 ; ATAXIA-TELANGIECTASIA ; THIOREDOXIN REDUCTASE ; IONIZING-RADIATION ; OXIDATIVE STRESS ; PROTEIN-KINASE ; POSTTRANSLATIONAL MODIFICATION
英文摘要

Histone deacetylase (HDAC) inhibitors have been proven to be effective therapeutic agents to kill cancer cells through inhibiting HDAC activity or altering the structure of chromatin. As a potent HDAC inhibitor, depsipeptide not only modulates histone deacetylation but also activates non-histone protein p53 to inhibit cancer cell growth. However, the mechanism of depsipeptide-induced p53 transactivity remains unknown. Here, we show that depsipeptide causes DNA damage through induction of reactive oxygen species (ROS) generation, as demonstrated by a comet assay and by detection of the phosphorylation of H2AX. Depsipeptide induced oxidative stress was confirmed to relate to a disturbance in reduction-oxidation (redox) reactions through inhibition of the transactivation of thioredoxin reductase (TrxR) in human cancer cells. Upon treatment with depsipeptide, p53 phosphorylation at threonine 18 (Thr18) was specifically induced. Furthermore, we also demonstrated that phosphorylation of p53 at Thr18 is required for p53 acetylation at lysine 373/382 and for p21 expression in response to depsipeptide treatment. Our results demonstrate that depsipeptide plays an anti-neoplastic role by generating ROS to elicit p53/p21 pathway activation. (C) 2011 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000301618900007
项目编号31071117 ; 90919030 ; 31070691 ; 30921062 ; 2011CB504200
资助机构National Natural Science Foundation of China ; Ministry of Science and Technology of China ; Beijing Natural Scicence Foundation
引用统计
被引频次:26[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/400002259/49874
专题北京大学基础医学院_病理学系
北京大学医学部管理机构_医学部
北京大学基础医学院
北京大学临床肿瘤学院_胸部肿瘤外二科
作者单位1.Peking Univ, Hlth Sci Ctr, Key Lab Carcinogenesis & Translat Res, Minist Educ,Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Biomed Teaching Lab Ctr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Wang, Haiying,Zhou, Wen,Zheng, Zhixing,et al. The HDAC inhibitor depsipeptide transactivates the p53/p21 pathway by inducing DNA damage[J]. DNA REPAIR,2012,11(2):146-156.
APA Wang, Haiying.,Zhou, Wen.,Zheng, Zhixing.,Zhang, Ping.,Tu, Bo.,...&Zhu, Wei-Guo.(2012).The HDAC inhibitor depsipeptide transactivates the p53/p21 pathway by inducing DNA damage.DNA REPAIR,11(2),146-156.
MLA Wang, Haiying,et al."The HDAC inhibitor depsipeptide transactivates the p53/p21 pathway by inducing DNA damage".DNA REPAIR 11.2(2012):146-156.
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