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学科主题: 基础医学
题名:
WW Domain-containing E3 Ubiquitin Protein Ligase 1 (WWP1) Delays Cellular Senescence by Promoting p27(Kip1) Degradation in Human Diploid Fibroblasts
作者: Cao, Xiaoxiao; Xue, Lixiang; Han, Limin; Ma, Liwei; Chen, Tianda; Tong, Tanjun
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2011-09-23
DOI: 10.1074/jbc.M111.225565
卷: 286, 期:38, 页:33447-33456
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: KRUPPEL-LIKE FACTOR ; CAENORHABDITIS-ELEGANS ; BREAST-CANCER ; PATHWAY ; TARGET ; TRANSCRIPTION ; BINDING ; CELLS ; RB
英文摘要:

WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) plays an important role in the proliferation of tumor cells and the lifespan of Caenorhabditis elegans. However, the role of WWP1 in cellular senescence is still unknown. Here, we show that the expression patterns of p27(Kip1) and WWP1 are inversely correlated during cellular senescence. Moreover, the overexpression of WWP1 delayed senescence, whereas the knockdown of WWP1 led to premature senescence in human fibroblasts. Furthermore, we demonstrate that WWP1 repressed endogenous p27(Kip1) expression through ubiquitin-proteasome-mediated degradation. Additionally, WWP1 had a strong preference for catalyzing the Lys-48-linked polyubiquitination of p27(Kip1) in vitro. Finally, we demonstrate that WWP1 markedly inhibited the replicative senescence induced by p27(Kip1) by promoting p27(Kip1) degradation. Therefore, our study provides a new molecular mechanism for the regulation of cellular senescence.

语种: 英语
所属项目编号: 2007CB507400 ; 30973146
项目资助者: Special Funds for Major State Basis Research of China ; National Natural Science Foundation of China
WOS记录号: WOS:000294968800062
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60805
Appears in Collections:基础医学院_北京大学衰老研究中心_期刊论文

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J. Biol. Chem.-2011-Cao-33447-56.pdf(2004KB)期刊论文作者接受稿限制开放 联系获取全文

作者单位: Peking Univ, Res Ctr Aging, Dept Biochem & Mol Biol, Hlth Sci Ctr, Beijing 100191, Peoples R China

Recommended Citation:
Cao, Xiaoxiao,Xue, Lixiang,Han, Limin,et al. WW Domain-containing E3 Ubiquitin Protein Ligase 1 (WWP1) Delays Cellular Senescence by Promoting p27(Kip1) Degradation in Human Diploid Fibroblasts[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(38):33447-33456.
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