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学科主题: 基础医学
题名:
p21(Waf1/Cip1) plays a critical role in modulating senescence through changes of DNA methylation
作者: Zheng, Quan Hui; Ma, Li Wei; Zhu, Wei Guo; Zhang, Zong Yu; Tong, Tan Jun
关键词: DNA methylation ; p21(Waf1/Cip1) ; p16(INK4a) ; senescence ; DNA methyltransferas
刊名: JOURNAL OF CELLULAR BIOCHEMISTRY
发表日期: 2006-08-01
DOI: 10.1002/jcb.20838
卷: 98, 期:5, 页:1230-1248
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: HUMAN-DIPLOID FIBROBLASTS ; CYCLIN-DEPENDENT KINASES ; INVITRO LIFE-SPAN ; RETINOBLASTOMA PROTEIN ; CELLULAR SENESCENCE ; METHYLTRANSFERASE INHIBITION ; TRANSCRIPTIONAL ACTIVATION ; ISLAND HYPERMETHYLATION ; REPLICATIVE SENESCENCE ; P16(INK4A) EXPRESSION
英文摘要:

It has been reported that genomic DNA methylation decreases gradually during cell culture and an organism′s aging. However, less is known about the methylation changes of age-related specific genes in aging. p21(Waf1/Cip1) and p16(INK4a) are cyclin-dependent kinase (Cdk) inhibitors that are critical for the replicative senescence of normal cells. In this study, we show that p21(Waf1/Cip1) and p16(INK4a) have different methylation patterns during the aging process of normal human 2BS and WI-38 fibroblasts. p21(Waf1/Cip1) promoter is gradually methylated up into middle-aged fibroblasts but not with senescent fibroblasts, whereas p16(INK4a) is always unmethylated in the aging process. Correspondently, the protein levels of DNA methyltransferase 1 (DNMT1) and DNMT3a increase from young to middle-aged fibroblasts but decrease in the senescent fibroblasts, while DNMT3b decreases stably from young to senescent fibroblasts. p21(Waf1/Cip1) promoter methylation directly represses its expression and blocks the radiation-induced DNA damage-signaling pathway by p53 in middle-aged fibroblasts. More importantly, demethylation by 5-aza-CdR or DNMT1 RNA interference (RNAi) resulted in an increased p21(Waf1/Cip1) level and premature senescence of middle-aged fibroblasts demonstrated by cell growth arrest and high beta-Galactosidase expression. Our results suggest that p21(Waf1/Cip1) but not p16(INK4a) is involved in the DNA methylation mediated aging process. p21(Waf1/Cip1) promoter methylation may be a critical biological barrier to postpone the aging process.

语种: 英语
WOS记录号: WOS:000239336800018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63542
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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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China
2.Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Beijing 100083, Peoples R China

Recommended Citation:
Zheng, Quan Hui,Ma, Li Wei,Zhu, Wei Guo,et al. p21(Waf1/Cip1) plays a critical role in modulating senescence through changes of DNA methylation[J]. JOURNAL OF CELLULAR BIOCHEMISTRY,2006,98(5):1230-1248.
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