学科主题基础医学
p21(Waf1/Cip1) plays a critical role in modulating senescence through changes of DNA methylation
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
2006-08-01
DOI10.1002/jcb.20838
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
引用统计
被引频次:41[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63542
专题北京大学基础医学院_北京大学衰老研究中心
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
推荐引用方式
GB/T 7714
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.
APA Zheng, Quan Hui,Ma, Li Wei,Zhu, Wei Guo,Zhang, Zong Yu,&Tong, Tan Jun.(2006).p21(Waf1/Cip1) plays a critical role in modulating senescence through changes of DNA methylation.JOURNAL OF CELLULAR BIOCHEMISTRY,98(5),1230-1248.
MLA Zheng, Quan Hui,et al."p21(Waf1/Cip1) plays a critical role in modulating senescence through changes of DNA methylation".JOURNAL OF CELLULAR BIOCHEMISTRY 98.5(2006):1230-1248.
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