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

doi:10.1021/acs.jproteome.7b00761

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	Glutaredoxin-1 Silencing Induces Cell Senescence via p53/p21/p16 Signaling Axis
	Yang, Fan 3; Yi, Meiqi 3; Liu, Yan 3; Wang, Qjngtao 2; Hu, Yadong 1,3; Deng, Haiteng 3
刊名	JOURNAL OF PROTEOME RESEARCH
	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
DOI	10.1021/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
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000426804300014
内容类型	期刊论文
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.Chinese Acad Sci, Chengdu Inst Biol, Renmin South Rd, Chengdu 610000, Sichuan, Peoples R China 2.Capital Med Univ, Beijing Chaoyang Hosp, Beijing 100020, Peoples R China; 3.Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, 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.