E2F-1 directly regulates thrombospondin 1 expression.
E2F-1 directly regulates thrombospondin 1 expression.
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DOI：
10.1371/journal.pone.0013442
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发表时间：
2010-10-15
期刊：
影响因子：
3.7
通讯作者：
Xiao W
中科院分区：
文献类型：
--
作者：
Ji W;Zhang W;Xiao W
血小板反应蛋白1（TSP 1）已被证明在抑制血管生成中起关键作用，从而抑制肿瘤生长和转移。弄清TSP 1的调控因子将有助于从机制上揭示其生物学功能。本研究通过启动子分析和北方印迹分析证实了E2 F-1能够激活TSP 1的转录。对各种TSP 1启动子突变体构建体的分析表明，位于转录起始位点上游-144/-137的序列（与共有E2 F应答序列相关）是激活所必需的。与过度表达E2 F-1上调TSP-1活性一致，内源性E2 F-1的敲低显著抑制TSP-1启动子活性，这意味着E2 F-1介导的TSP-1调节与体内相关。此外，E2 F-1也可以直接结合到覆盖-144/-137区域的TSP 1启动子区域。此外，E2 F-1诱导的TSP 1基因转录的激活被pRB 1以剂量依赖性方式抑制。总而言之，结果表明TSP 1是E2 F1的新靶点，这可能意味着E2 F-1可以通过调节TSP 1表达来影响血管生成。
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.
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DOI：
10.1083/jcb.200109098
发表时间：
2002-04-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Li Z;Calzada MJ;Sipes JM;Cashel JA;Krutzsch HC;Annis DS;Mosher DF;Roberts DD
通讯作者：
Roberts DD
DOI：
10.1083/jcb.138.3.707
发表时间：
1997-08-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
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影响因子：
30.8
作者：
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通讯作者：
Korsmeyer, SJ
影响因子：
6
作者：
Lawler, J;Miao, WM;Hynes, RO
通讯作者：
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影响因子：
5.6
作者：
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通讯作者：
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