Juven T, Barak Y, Zauberman A, George D L, Oren M
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Oncogene. 1993 Dec;8(12):3411-6.
The p53 tumor suppressor gene product can complex with polypeptides encoded by the mdm2 putative protoncogene. In addition, mdm2 mRNA levels have been shown to increase following the activation of wild type (wt) p53. To determine the basis for the effect of wt p53 on mdm2 mRNA, we studied the interaction of the mdm2 gene with p53. We report that wt p53 can bind sequence-specifically to a DNA region residing downstream to exon 1 of the mdm2 gene. This is correlated with a pronounced p53-dependent transcriptional activation. Efficient p53-dependent transactivation can be obtained with an mdm2 genomic DNA fragment lacking the putative mdm2 promoter. These findings suggest that p53 can induce transcription from an internal promoter located within the mdm2 gene. These findings raise the possibility that, in addition to increasing the overall levels of mdm2 mRNA, wt p53 may also modulate the repertoire of mdm2 transcripts present within the cell.
p53肿瘤抑制基因产物可与由mdm2假定原癌基因编码的多肽形成复合物。此外，已表明野生型（wt）p53激活后mdm2 mRNA水平会升高。为了确定wt p53对mdm2 mRNA产生影响的基础，我们研究了mdm2基因与p53的相互作用。我们报告称，wt p53可序列特异性地结合到mdm2基因外显子1下游的一个DNA区域。这与明显的p53依赖性转录激活相关。使用缺乏假定mdm2启动子的mdm2基因组DNA片段可实现有效的p53依赖性反式激活。这些发现表明，p53可诱导来自mdm2基因内一个内部启动子的转录。这些发现增加了一种可能性，即除了提高mdm2 mRNA的总体水平外，wt p53还可能调节细胞内存在的mdm2转录本种类。
