Jacob Joby, Cabarcas Stephanie, Veras Ingrid, Zaveri Nurulain, Schramm Laura
Department of Biological Sciences, St. John's University, Queens, NY 11439, USA.
Biochem Biophys Res Commun. 2007 Sep 7;360(4):778-83. doi: 10.1016/j.bbrc.2007.06.114. Epub 2007 Jul 2.
RNA polymerase III (RNA pol III) transcribes many small structural RNA molecules involved in RNA processing and translation, and thus regulates the growth rate of a cell. Accurate initiation by RNA pol III requires the initiation factor TFIIIB. TFIIIB has been demonstrated to be regulated by tumor suppressors, including ARF, p53, RB, and the RB-related pocket proteins, and is a target of the oncogene c-myc and the mitogen-activated protein kinase ERK. EGCG has been demonstrated to inhibit the growth of a variety of cancer cells, induce apoptosis and regulate the expression of p53, myc, and ERK. Thus, we hypothesized that EGCG may regulate RNA pol III transcription in cells. Here, we report that EGCG (1) inhibits RNA pol III transcription from gene internal and gene external promoters (2) EGCG inhibits protein expression of the TFIIIB subunits Brf1 and Brf2, and (3) EGCG inhibits Brf2 promoter activity in cervical carcinoma cells.
RNA聚合酶III(RNA pol III)转录许多参与RNA加工和翻译的小结构RNA分子,从而调节细胞的生长速率。RNA pol III的准确起始需要起始因子TFIIIB。已证明TFIIIB受肿瘤抑制因子调节,包括ARF、p53、RB以及与RB相关的口袋蛋白,并且是癌基因c-myc和丝裂原活化蛋白激酶ERK的作用靶点。表没食子儿茶素没食子酸酯(EGCG)已被证明可抑制多种癌细胞的生长、诱导细胞凋亡并调节p53、myc和ERK的表达。因此,我们推测EGCG可能在细胞中调节RNA pol III转录。在此,我们报告EGCG(1)抑制来自基因内部和基因外部启动子的RNA pol III转录,(2)EGCG抑制TFIIIB亚基Brf1和Brf2的蛋白表达,以及(3)EGCG抑制子宫颈癌细胞中Brf2启动子活性。