Regulation of the cdk inhibitor p21 gene during cell cycle progression is under the control of the transcription factor E2F
Regulation of the cdk inhibitor p21 gene during cell cycle progression is under the control of the transcription factor E2F
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DOI：
10.1038/sj.onc.1201667
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发表时间：
1998-03-26
期刊：
影响因子：
8
通讯作者：
Reeves, SA
中科院分区：
文献类型：
--
作者：
Hiyama, H;Iavarone, A;Reeves, SA
细胞周期进程的控制是由一个非常多样化和动态的蛋白质功能组协调的。E2 F家族的转录因子调节G（1）/S转换所必需的基因的表达，WAF/CIP/KIP家族的cdk抑制剂可以抑制细胞周期进程。在这份报告中，我们已经确定了E2 F结合位点的人类和小鼠p21启动子结合E2 F蛋白复合物从核提取物中的细胞周期依赖性的方式。在异位表达实验中，我们确定E2 F1，而不是E2 F4，可以通过这些位于p21基因的-215/+1区域的E2 F结合位点强烈地反式激活人p21基因。p21基因通过启动子-215/+1区域内的调节元件的反式激活与G（1）/S边界处内源性E2 F1和p21蛋白水平的增加相关。E2 F反式激活p21基因的意义在于p21功能在细胞周期进程中以及对于细胞周期停滞都是重要的。事实上，E2 F诱导的p21蛋白水平在G（1）/S转换是一致的，最近的研究结果表明，p21作为一个组装因子的激酶活性细胞周期蛋白/cdk/p21复合物。
The control of cell cycle progression is orchestrated by an extraordinary diverse and dynamic in function group of proteins. Critical in the progression are the actions of the E2F family of transcription factors which regulate the expression of genes necessary for the G(1)/S transition and the WAF/CIP/KIP family of cdk inhibitors which can inhibit cell cycle progression. In this report, we have identified E2F binding sites in both the human and mouse p21 promoters that bind E2F protein complexes from nuclear extracts in a cell cycle-dependent manner. In ectopic expression experiments we determined that E2F1, but not E2F4, can strongly transactivate the human p21 gene through these E2F binding sites which are located in the -215/+1 region of the p21 gene. The transactivation of the p21 gene through regulatory elements within the -215/+1 region of the promoter was correlated with increased levels of endogenous E2F1 and p21 proteins at the G(1)/S boundary. The significance of transactivation of the p21 gene by E2F is that p21 function is important in cell cycle progression as well as for cell cycle arrest. Indeed, E2F- induced levels of p21 protein during the G(1)/S transition is consistent with the recent findings demonstrating that p21 acts as an assembly factor for kinase active cyclin/cdk/p21 complexes.