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学科主题: 基础医学
题名:
Upregulation of SIRT1 by 17 beta-estradiol depends on ubiquitin-proteasome degradation of PPAR-gamma mediated by NEDD4-1
作者: Han, Limin1,2; Wang, Pan1,2; Zhao, Ganye1,2; Wang, Hui1,2; Wang, Meng1,2; Chen, Jun1,2; Tong, Tanjun1,2
关键词: 17 beta-estradiol ; PPAR gamma ; senescence ; SIRT1 ; ubiquitination
刊名: PROTEIN & CELL
发表日期: 2013-04-01
DOI: 10.1007/s13238-013-2124-z
卷: 4, 期:4, 页:310-321
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: ACTIVATED RECEPTOR-GAMMA ; PROTEIN-KINASE ; SYSTEM CONTROLS ; PHOSPHORYLATION ; SENESCENCE ; ALPHA ; ADIPOGENESIS ; ADIPOCYTES ; EXPRESSION ; LIGANDS
英文摘要:

17 beta-estradiol (E2) treatment of cells results in an upregulation of SIRT1 and a down-regulation of PPAR gamma. The decrease in PPAR gamma expression is mediated by increased degradation of PPAR gamma. Here we report that PPAR gamma is ubiquitinated by HECT E3 ubiquitin ligase NEDD4-1 and degraded, along with PPAR gamma, in response to E2 stimulation. The PPAR gamma interacts with ubiquitin ligase NEDD4-1 through a conserved PPXY-WW binding motif. The WW3 domain in NEDD4-1 is critical for binding to PPARI". NEDD4-1 overexpression leads to PPAR gamma ubiquitination and reduced expression of PPAR gamma. Conversely, knockdown of NEDD4-1 by specific siRNAs abolishes PPARI" ubiquitination. These data indicate that NEDD4-1 is the E3 ubiquitin ligase responsible for PPAR gamma ubiquitination. Here, we show that NEDD4-1 delays cellular senescence by degrading PPARI" expression. Taken together, our data show that E2 could upregulate SIRT1 expression via promoting the PPARI" ubiquitination-proteasome degradation pathway to delay the process of cell senescence.

语种: 英语
所属项目编号: 2012CB911203 ; 2013CB530801 ; 31100997 ; 20100470169
项目资助者: National Basic Research Programs of China ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation
WOS记录号: WOS:000317018000009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52187
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Peking Univ Res Ctr Aging, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Sch Basic Med, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China

Recommended Citation:
Han, Limin,Wang, Pan,Zhao, Ganye,et al. Upregulation of SIRT1 by 17 beta-estradiol depends on ubiquitin-proteasome degradation of PPAR-gamma mediated by NEDD4-1[J]. PROTEIN & CELL,2013,4(4):310-321.
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