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学科主题: 基础医学
题名:
Characterization of a novel positive transcription regulatory element that differentially regulates the alpha-2-macroglobulin gene in replicative senescence
作者: Li, Renzhong; Ma, Liwei; Huang, Yu; Zhang, Zongyu; Tong, Tanjun
关键词: Alpha-2-macroglobulin ; Senescence ; ATEE
刊名: BIOGERONTOLOGY
发表日期: 2011-12-01
DOI: 10.1007/s10522-011-9339-2
卷: 12, 期:6, 页:517-525
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Geriatrics & Gerontology
研究领域[WOS]: Geriatrics & Gerontology
关键词[WOS]: BETA-AMYLOID PEPTIDE ; BINDING-PROTEIN ; GROWTH-FACTOR ; OLD RATS ; ALPHA(2)-MACROGLOBULIN ; EXPRESSION ; FIBROBLASTS ; WILLIS ; CIRCLE ; STAT3
英文摘要:

Alpha-2-macroglobulin (alpha 2M), a protease inhibitor, is implicated in Alzheimer′s disease, atherosclerosis, and other age-related diseases. The elevated level of alpha 2M mRNA has been described in replicative senescence and it could be used as a biomarker of the aging cells. However, the mechanism responsible for the up-regulation of its expression is still unclear. This report identified a novel transcriptional regulatory element, the alpha 2M transcription enhancement element (ATEE), within the alpha 2M promoter. This element differentially activates alpha 2M expression in senescent versus young fibroblasts. Electrophoretic mobility shift assays revealed abundant complexes in senescent cell nuclear extracts compared with young cell nuclear extracts. The DNase I footprint revealed the protein-binding core sequence through which the protein binds the ATEE. Mutation within ATEE selectively abolished alpha 2M promoter activity in senescent (but not young) cells. These results indicated the ATEE, as a positive transcription regulatory element, contributes to the up-regulation of alpha 2M during replicative senescence.

语种: 英语
所属项目编号: 2007CB507400 ; 30973146 ; 31000609 ; 20090001120044
项目资助者: National Basic Research Programs of China ; National Natural Science Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education (SRFDP) of China
WOS记录号: WOS:000296633300003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58225
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: Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China

Recommended Citation:
Li, Renzhong,Ma, Liwei,Huang, Yu,et al. Characterization of a novel positive transcription regulatory element that differentially regulates the alpha-2-macroglobulin gene in replicative senescence[J]. BIOGERONTOLOGY,2011,12(6):517-525.
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