IR@PKUHSC  > 北京大学基础医学院  > 北京大学衰老研究中心
学科主题基础医学
The Retinoblastoma Protein Selectively Represses E2F1 Targets via a TAAC DNA Element during Cellular Senescence
Chen, Tianda; Xue, Lixiang; Niu, Jing; Ma, Liwei; Li, Na; Cao, Xiaoxiao; Li, Qian; Wang, Meng; Zhao, Wenting; Li, Guodong; Wang, Jiamu; Tong, Tanjun
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2012-10-26
DOI10.1074/jbc.M111.260679
287期:44页:37540-37551
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
资助者National Basic Research Programs of China ; National Natural Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China ; National Basic Research Programs of China ; National Natural Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]HUMAN FIBROBLASTS ; TUMOR-SUPPRESSOR ; HETEROCHROMATIN FORMATION ; REPLICATIVE SENESCENCE ; GENES ; CYCLE ; PROLIFERATION ; ACTIVATION ; P27(KIP1) ; MYB
英文摘要

The retinoblastoma (Rb) protein mediates heterochromatin formation at the promoters of E2 transcription factor 1 (E2F1) target genes, such as proliferating cell nuclear antigen and cyclin A2 (CCNA2), and represses these genes during cellular senescence. However, the selectivity of Rb recruitment is still not well understood. Here, we demonstrate that a senescence-associated gene is a direct target of E2F1 and is also repressed by heterochromatin in senescent cells. In contrast, ARF and p27(KIP1), which are also E2F1 targets, are not repressed by Rb and heterochromatin formation. By comparing the promoter sequences of these genes, we found a novel TAAC element that is present in the cellular senescence-inhibited gene, proliferating cell nuclear antigen, and CCNA2 promoters but absent from the ARF and p27KIP1 promoters. This TAAC element associates with Rb and is required for Rb recruitment. We further determined that TAAC element-mediated Rb association requires the E2F1 binding site, but not E2F1 protein. These results provide a novel molecular mechanism for the different expression patterns of E2F1 targets and afford new mechanistic insight regarding the selectivity of Rb-mediated heterochromatin formation and gene repression during cellular senescence.

语种英语
所属项目编号2012CB911200 ; 2013CB530801 ; 30973146 ; 31000609 ; 31071206 ; 20090001120044
资助者National Basic Research Programs of China ; National Natural Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China ; National Basic Research Programs of China ; National Natural Science Foundation of China ; Ministry of Education of the People&prime ; s Republic of China
WOS记录号WOS:000310588500082
Citation statistics
Cited Times:12[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55750
Collection北京大学基础医学院_北京大学衰老研究中心
作者单位Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
Recommended Citation
GB/T 7714
Chen, Tianda,Xue, Lixiang,Niu, Jing,et al. The Retinoblastoma Protein Selectively Represses E2F1 Targets via a TAAC DNA Element during Cellular Senescence[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(44):37540-37551.
APA Chen, Tianda.,Xue, Lixiang.,Niu, Jing.,Ma, Liwei.,Li, Na.,...&Tong, Tanjun.(2012).The Retinoblastoma Protein Selectively Represses E2F1 Targets via a TAAC DNA Element during Cellular Senescence.JOURNAL OF BIOLOGICAL CHEMISTRY,287(44),37540-37551.
MLA Chen, Tianda,et al."The Retinoblastoma Protein Selectively Represses E2F1 Targets via a TAAC DNA Element during Cellular Senescence".JOURNAL OF BIOLOGICAL CHEMISTRY 287.44(2012):37540-37551.
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