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Alien抑制E2F1基因表达和细胞增殖。

Alien inhibits E2F1 gene expression and cell proliferation.

作者信息

Tenbaum Stephan P, Papaioannou Maria, Reeb Christina A, Goeman Frauke, Escher Niko, Kob Robert, von Eggeling Ferdinand, Melle Christian, Baniahmad Aria

机构信息

Molecular Genetics, Institute of Human Genetics and Anthropology, Friedrich-Schiller-University, 07740 Jena, Germany.

出版信息

Biochim Biophys Acta. 2007 Sep;1773(9):1447-54. doi: 10.1016/j.bbamcr.2007.04.017. Epub 2007 May 10.

Abstract

Recently, using a proteomic approach we have identified the corepressor Alien as a novel interacting factor of the cell cycle regulator E2F1. Unclear was whether this interaction influences cell proliferation and endogenous E2F1 target gene expression. Here, we show by chromatin immunoprecipitation (ChIP) that Alien is recruited in vivo to the E2F binding sites present in the E2F1 gene promoter, inhibits the transactivation of E2F1 and represses endogenous E2F1 gene expression. Interestingly, using synchronized cells to assess the expression of Alien profile during cell cycle the levels of endogenous Alien are increased during G1, G1/S and G2 phase. Furthermore, stable transfection of Alien leads to reduction of cell proliferation. Thus, the data suggest that Alien acts as a corepressor for E2F1 and is involved in cell cycle regulation.

摘要

最近,我们采用蛋白质组学方法鉴定出共抑制因子Alien是细胞周期调节因子E2F1的一种新型相互作用因子。尚不清楚这种相互作用是否会影响细胞增殖和内源性E2F1靶基因的表达。在此,我们通过染色质免疫沉淀(ChIP)表明,Alien在体内被招募至E2F1基因启动子中存在的E2F结合位点,抑制E2F1的反式激活并抑制内源性E2F1基因的表达。有趣的是,使用同步化细胞来评估细胞周期中Alien的表达谱,内源性Alien的水平在G1期、G1/S期和G2期升高。此外,Alien的稳定转染导致细胞增殖减少。因此,数据表明Alien作为E2F1的共抑制因子参与细胞周期调控。

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