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题名: E2F-1 Directly Regulates Thrombospondin 1 Expression
作者: Ji, Wei1; Zhang, Wei1; Xiao, Wuhan1
通讯作者: Ji, W, Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan, Peoples R China
关键词: CELL-CYCLE CONTROL ; ENDOTHELIAL-CELLS ; RB/E2F PATHWAY ; LEUKEMIA ; MICE ; ANGIOGENESIS ; GENE ; MLL ; APOPTOSIS ; CD36
刊名: PLOS ONE
发表日期: 2010-10-15
DOI: 10.1371/journal.pone.0013442
卷: 5, 期:10, 页:-e13442
收录类别: SCI
文章类型: Article
部门归属: [Ji, Wei; Zhang, Wei; Xiao, Wuhan] Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan, Peoples R China
WOS标题词: Science & Technology
资助者: 973'' grant [2010CB126306, 2007CB815705, 2006CB504102]; Natural Science Foundation of China (NSFC) [31071211, 30971667, 30890113]; National Transgene Project [2009ZX08010-021B] W.X. is supported by 973'' grant 2010CB126306, 2007CB815705, 2006CB504102, Natural Science Foundation of China (NSFC) grant 31071211, 30971667, 30890113 and National Transgene Project 2009ZX08010-021B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
摘要: Thrombospondin 1 (TSP1) has been shown to play a critical role in inhibiting angiogenesis, resulting in inhibition of tumor growth and metastases. To figure out TSP1's regulators will lead to reveal its biological function mechanistically. In this study, we show that E2F-1 could activate the transcription of TSP1 by both promoter assays and Northern blot. Analysis of various TSP1 promoter mutant constructs showed that a sequence located -144/-137 up-stream of the transcriptional initiation site, related to the consensus E2F-responsive sequence, is necessary for the activation. In consistence with up-regulation of TSP-1 activity by over-expression of E2F-1, the knockdown of endogenous E2F-1 inhibited TSP-1 promoter activity significantly, implying that E2F-1 mediated regulation of TSP-1 is relevant in vivo. In addition, E2F-1 could also directly bind to the TSP1 promoter region covering -144/-137 region as revealed by ChIP assays. Furthermore, the E2F-1-induced activation of TSP1 gene transcription is suppressed by pRB1 in a dose-dependent manner. Taken together, the results demonstrate that TSP1 is a novel target for E2F1, which might imply that E2F-1 can affect angiogenesis by modulating TSP1 expression.
英文摘要: Thrombospondin 1 (TSP1) has been shown to play a critical role in inhibiting angiogenesis, resulting in inhibition of tumor growth and metastases. To figure out TSP1's regulators will lead to reveal its biological function mechanistically. In this study, we show that E2F-1 could activate the transcription of TSP1 by both promoter assays and Northern blot. Analysis of various TSP1 promoter mutant constructs showed that a sequence located -144/-137 up-stream of the transcriptional initiation site, related to the consensus E2F-responsive sequence, is necessary for the activation. In consistence with up-regulation of TSP-1 activity by over-expression of E2F-1, the knockdown of endogenous E2F-1 inhibited TSP-1 promoter activity significantly, implying that E2F-1 mediated regulation of TSP-1 is relevant in vivo. In addition, E2F-1 could also directly bind to the TSP1 promoter region covering -144/-137 region as revealed by ChIP assays. Furthermore, the E2F-1-induced activation of TSP1 gene transcription is suppressed by pRB1 in a dose-dependent manner. Taken together, the results demonstrate that TSP1 is a novel target for E2F1, which might imply that E2F-1 can affect angiogenesis by modulating TSP1 expression.
关键词[WOS]: CELL-CYCLE CONTROL ; ENDOTHELIAL-CELLS ; RB/E2F PATHWAY ; LEUKEMIA ; MICE ; ANGIOGENESIS ; GENE ; MLL ; APOPTOSIS ; CD36
语种: 英语
WOS记录号: WOS:000283043700027
ISSN号: 1932-6203
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/13751
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Biodivers & Conservat Aquat Organisms, Wuhan, Peoples R China

Recommended Citation:
Ji, Wei; Zhang, Wei; Xiao, Wuhan.E2F-1 Directly Regulates Thrombospondin 1 Expression,PLOS ONE,2010,5(10):-e13442
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