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Glutaredoxin-1 Silencing Induces Cell Senescence via p53/p21/p16 Signaling Axis

文献类型：期刊论文

作者Yang, Fan1; Yi, Meiqi1; Liu, Yan1; Wang, Qjngtao2; Hu, Yadong1,3; Deng, Haiteng1
刊名JOURNAL OF PROTEOME RESEARCH
出版日期2018-03-01
卷号17期号:3页码:1091-1100
关键词Glutaredoxin-1 S-glutathionylation cell senescence proteomics redox signaling
ISSN号1535-3893
DOI10.1021/acs.jproteome.7b00761
产权排序3
文献子类Article
英文摘要Glutaredoxin-1 (Grxl) catalyzes deglutathionylation with glutathione as a cofactor. Accumulating evidence indicates important roles for Grxl and S-glutathionylation in the aging process; however, further exploration of Grxl-regulated cellular processes is important to understand the functions of Grxl in aging. In the present study, we constructed stable Grxl knockdown or overexpression human cell lines. Grxl silencing significantly decreased the cellular ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) (GSH/GSSG ratio), resulting in excessive reactive oxygen species (ROS) accumulation, whereas Grxl overexpression decreased cellular ROS levels. Grxl silencing also increased glutathionylation of DJ-1 and HSP60, contributing to decreased mitochondrial spare respiration capacity and ATP production. We applied quantitative proteomics to identify differentially expressed proteins between Grxl knockdown and control cells and showed that Grxl silencing inactivated DNA replication and damage repair pathways. p53 signaling was activated by Grxl silencing, which inhibited the CDK4-mediated G1-S transition, resulting in GI phase cell-cycle arrest and cell senescence, a known hallmark of aging. Taken together, our results indicate that Grxl regulates DNA replication and damage repair processes and is a potential therapeutic target for aging-related diseases.
学科主题Chemistry ; Analysis
URL标识查看原文
WOS关键词PROTEIN GLUTATHIONYLATION ; RESPIRATORY CAPACITY ; OXIDATIVE STRESS ; DJ-1 ; THIOLTRANSFERASE ; HOMEOSTASIS ; MECHANISMS ; PRELAMIN ; ARREST ; P21
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000426804300014
出版者AMER CHEMICAL SOC
源URL[http://210.75.237.14/handle/351003/30306]  
专题环境治理与食品安全领域_农业生物技术研究
作者单位1.Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China;
2.Capital Med Univ, Beijing Chaoyang Hosp, Beijing 100020, Peoples R China;
3.Chinese Acad Sci, Chengdu Inst Biol, Renmin South Rd, Chengdu 610000, Sichuan, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Fan,Yi, Meiqi,Liu, Yan,et al. Glutaredoxin-1 Silencing Induces Cell Senescence via p53/p21/p16 Signaling Axis[J]. JOURNAL OF PROTEOME RESEARCH,2018,17(3):1091-1100.
APA Yang, Fan,Yi, Meiqi,Liu, Yan,Wang, Qjngtao,Hu, Yadong,&Deng, Haiteng.(2018).Glutaredoxin-1 Silencing Induces Cell Senescence via p53/p21/p16 Signaling Axis.JOURNAL OF PROTEOME RESEARCH,17(3),1091-1100.
MLA Yang, Fan,et al."Glutaredoxin-1 Silencing Induces Cell Senescence via p53/p21/p16 Signaling Axis".JOURNAL OF PROTEOME RESEARCH 17.3(2018):1091-1100.

入库方式： OAI收割

来源：成都生物研究所

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