中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 国家新药筛选中心
Intact MDM2 E3 ligase activity is required for the cytosolic localization and function of beta-arrestin2

文献类型：期刊论文

作者Yin, Chenlei1,2; Zhang, Ru1; Xu, Yongyu1,2; Chen, Qiuyan1,2; Xie, Xin1,2
刊名MOLECULAR BIOLOGY OF THE CELL
出版日期2011-05-01
卷号22期号:9页码:1608-1616
ISSN号1059-1524
DOI10.1091/mbc.E10-09-0779
文献子类Article
英文摘要beta-arrestins are well known for their roles in desensitization and sequestration of G protein-coupled receptors. Unlike beta-arrestin1, beta-arrestin2 exhibits a predominant cytoplasmic distribution at steady state. However, the mechanism and functional significance underlying the regulation of beta-arrestin2 subcellular localization remains undefined. Here we report that the subcellular localization and function of beta-arrestin2 is tightly regulated by Mdm2 E3 ligase activity. Inhibition of Mdm2 E3 ligase activity either by expressing Mdm2 RING finger mutants or using specific Mdm2 E3 ligase inhibitor is sufficient to stabilize the Mdm2/beta-arrestin2 complex and cause abnormal nuclear localization of beta-arrestin2. Next we demonstrate that lysine residues at position 11 and 12 of beta-arrestin2 are required for the interaction between Mdm2 RING finger mutant H457S (Mdm2(H457S)) and beta-arrestin2, mutation of which prevents Mdm2(H457S)/beta-arrestin2 interaction and subsequent nuclear localization of beta-arrestin2. Finally, beta-arrestin2-dependent signalings, such as receptor internalization and extracellular signal-regulated protein kinase activation, are found to be impaired once the beta-arrestin2 is sequestered in the nuclei by Mdm2(H457S). Our findings depict the essential role of Mdm2 E3 ligase activity in determining beta-arrestin2 subcellular localization and corresponding signaling.
WOS关键词NUCLEAR EXPORT SIGNAL ; BETA-ARRESTIN ; ONCOPROTEIN MDM2 ; RECEPTOR ; PROTEIN ; P53 ; UBIQUITINATION ; ACTIVATION ; TRANSCRIPTION ; TRAFFICKING
资助项目Ministry of Science and Technology of China[2008DFB30150] ; National Natural Science Foundation of China[31071227] ; Shanghai Commission of Science and Technology[08410703500] ; Shanghai Commission of Science and Technology[08431910100] ; Shanghai Commission of Science and Technology[09PJ1410000] ; Shanghai Commission of Science and Technology[09DZ2260100] ; Shanghai Commission of Science and Technology[2010CB944901] ; Shanghai Commission of Science and Technology[2011CB965104] ; Roche RRDCC Basic Research Grant[00000000]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000290023700018
出版者AMER SOC CELL BIOLOGY
源URL[http://119.78.100.183/handle/2S10ELR8/278549]  
专题国家新药筛选中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Xie, Xin
作者单位1.Tongji Univ, Shanghai Key Lab Signaling & Dis Res, Lab Receptor Based Biomed, Sch Life Sci & Technol, Shanghai 200092, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Yin, Chenlei,Zhang, Ru,Xu, Yongyu,et al. Intact MDM2 E3 ligase activity is required for the cytosolic localization and function of beta-arrestin2[J]. MOLECULAR BIOLOGY OF THE CELL,2011,22(9):1608-1616.
APA Yin, Chenlei,Zhang, Ru,Xu, Yongyu,Chen, Qiuyan,&Xie, Xin.(2011).Intact MDM2 E3 ligase activity is required for the cytosolic localization and function of beta-arrestin2.MOLECULAR BIOLOGY OF THE CELL,22(9),1608-1616.
MLA Yin, Chenlei,et al."Intact MDM2 E3 ligase activity is required for the cytosolic localization and function of beta-arrestin2".MOLECULAR BIOLOGY OF THE CELL 22.9(2011):1608-1616.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。