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CDF-1介导的细胞周期基因抑制作用靶向特定的反式激活因子亚群。

CDF-1 mediated repression of cell cycle genes targets a specific subset of transactivators.

作者信息

Zwicker J, Lucibello F C, Jérôme V, Brüsselbach S, Müller R

机构信息

Institut für Molekularbiologie und Tumorforschung (IMT), Phillipps-Universität Marburg, Germany.

出版信息

Nucleic Acids Res. 1998 Feb 15;26(4):4926-32.

Abstract

The cdc25C, cyclin A and cdc2 genes are regulated during the cell cycle through two contiguous repressor binding sites, the CDE and CHR, located in the region of transcription initiation and interacting with a factor termed CDF-1. The target of this repression seems to be transcriptional activation of these promoters by transcription factors bound upstream. The majority of these factors falls into the class of glutamine-rich activators, suggesting that CDF-1-mediated repression might be activation domain specific. In the present study we have used chimeric promoter constructs to demonstrate that the cdc25C UAS, but not the core promoter, is crucial for repression. In addition, we show that only specific transcription factors and activation domains are responsive to CDE-CHR-mediated cell cycle regulation. These observations clearly indicate that CDF-1 interferes with activation of transcription by a specific subset of transactivators. The repressible activation domains belong to the same class of glutamine-rich activators, pointing to specific interactions of CDF-1 with components of the transcription machinery. In agreement with this conclusion we find that a simple inversion of the CDF-CHR module completely abrogates cell cycle-regulated repression.

摘要

细胞分裂周期蛋白25C(cdc25C)、细胞周期蛋白A和细胞分裂周期蛋白2(cdc2)基因在细胞周期中通过两个相邻的阻遏物结合位点进行调控,这两个位点即细胞分裂周期基因元件(CDE)和细胞分裂周期同源区(CHR),它们位于转录起始区域,并与一种名为细胞分裂周期基因因子1(CDF-1)的因子相互作用。这种抑制作用的靶点似乎是上游结合的转录因子对这些启动子的转录激活。这些因子大多数属于富含谷氨酰胺的激活因子类别,这表明CDF-1介导的抑制作用可能具有激活域特异性。在本研究中,我们使用嵌合启动子构建体来证明,cdc25C上游激活序列(UAS)而非核心启动子,对抑制作用至关重要。此外,我们表明只有特定的转录因子和激活域对CDE-CHR介导的细胞周期调控有反应。这些观察结果清楚地表明,CDF-1通过特定的反式激活因子子集干扰转录激活。可被抑制的激活域属于同一类富含谷氨酰胺的激活因子,这表明CDF-1与转录机制的成分存在特定相互作用。与这一结论一致,我们发现CDF-CHR模块的简单倒置完全消除了细胞周期调控的抑制作用。

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