Gopalkrishnan R V, Lam E W, Kedinger C
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM, University Louis Pasteur), F-67404 Illkirch Cedex C.U. de Strasbourg, France.
J Biol Chem. 1998 May 1;273(18):10972-8. doi: 10.1074/jbc.273.18.10972.
Cell cycle progression is subject to several regulatory controls, of which the p53 protein plays a major role in growth arrest, subsequent to the detection of cellular aberrations. It is well documented that p53 has the ability to inhibit transcription driven by several promoters, possibly via distinct mechanisms. In this report, we show that expression of the cell cycle regulatory transcription factor DP1 is strongly inhibited by p53, at the level of transcription and probably through the basal TATA-less promoter. This inhibitory activity has a relative specificity for the DP1 promoter compared with the functionally related E2F1 promoter or unrelated promoters such as those of the transcription factor ATFa or the thymidine kinase gene. Inhibition of DP1 transcription has implications in one of the several possible mechanisms through which p53 induces cell cycle arrest.
细胞周期进程受到多种调控机制的控制,其中p53蛋白在检测到细胞异常后导致生长停滞的过程中发挥着主要作用。有充分的文献记载,p53能够通过多种不同机制抑制多个启动子驱动的转录。在本报告中,我们表明细胞周期调控转录因子DP1的表达在转录水平上受到p53的强烈抑制,可能是通过无TATA框的基础启动子。与功能相关的E2F1启动子或不相关的启动子(如转录因子ATFa或胸苷激酶基因的启动子)相比,这种抑制活性对DP1启动子具有相对特异性。抑制DP1转录是p53诱导细胞周期停滞的几种可能机制之一。