Intact MDM2 E3 ligase activity is required for the cytosolic localization and function of beta-arrestin2 | |
Yin, Chenlei1,2; Zhang, Ru1; Xu, Yongyu1,2; Chen, Qiuyan1,2; Xie, Xin1,2![]() | |
刊名 | MOLECULAR BIOLOGY OF THE CELL
![]() |
2011-05-01 | |
卷号 | 22期号:9页码:1608-1616 |
ISSN号 | 1059-1524 |
DOI | 10.1091/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. |
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关键词 | NUCLEAR EXPORT SIGNAL ; BETA-ARRESTIN ; ONCOPROTEIN MDM2 ; RECEPTOR ; PROTEIN ; P53 ; UBIQUITINATION ; ACTIVATION ; TRANSCRIPTION ; TRAFFICKING |
WOS研究方向 | Cell Biology |
语种 | 英语 |
出版者 | AMER SOC CELL BIOLOGY |
WOS记录号 | WOS:000290023700018 |
内容类型 | 期刊论文 |
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. |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
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。
修改评论