Cell‐cycle‐dependent regulation of the human and mouse Tome‐1 promoters

Cell‐cycle‐dependent regulation of the human and mouse Tome‐1 promoters
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DOI:
10.1016/j.febslet.2005.01.055
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发表时间:
2005-02
期刊:
影响因子:
3.5
通讯作者:
Kenichi Yoshida
Kenichi Yoshida
中科院分区:
生物学3区
文献类型:
--
作者:
Kenichi Yoshida

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TOME-1指的是有丝分裂进入1的触发物,通过E3连接酶SCF介导有丝分裂抑制激酶Wee1的破坏。反过来,Tome-1本身也是APC在细胞周期的G1期降解的目标。在本研究中,我们分析了人和小鼠Tome-1启动子区域。用Tome-1启动子/荧光素酶构建的NIH3T3细胞的同步培养,我们发现Tome-1的启动子活性在G2/M期被激活。利用不同的TOME-1启动子/荧光素酶结构,我们发现位于转录起始点上游的CCAAT盒对于基本启动子的活性是重要的。我们在转录起始点附近发现了一个抑制元件(细胞周期依赖元件/细胞周期基因同源区),该元件内的突变降低了TOME-1对细胞周期依赖的转录调控。
Tome-1, which refers to a trigger of mitotic entry 1, mediates the destruction of the mitosis-inhibitory kinase, Wee1, via the E3 ligase, SCF. In turn, Tome-1 itself is targeted for degradation by APC in the G1 phase of the cell cycle. In the present study, we analyzed the human and mouse Tome-1 promoter regions. Using synchronized cultures of NIH3T3 cells transfected with Tome-1 promoter/luciferase constructs, we showed that the promoter activity of Tome-1 is activated at the G2/M phase. Using various Tome-1 promoter/luciferase constructs, we showed that the CCAAT box located upstream of the transcription initiation site is important for the basal promoter activity. We identified a repressor element (cell-cycle-dependent element/cell cycle gene homology region) in the vicinity of the transcription start site, and mutations within this element diminished the cell-cycle-dependent transcriptional regulation of Tome-1.