Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene.
Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene.
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发表时间：
1993-12
期刊：
影响因子：
8
通讯作者：
T. Juven;Yoav Barak;A. Zauberman;George Dl;M. Oren
中科院分区：
文献类型：
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作者：
T. Juven;Yoav Barak;A. Zauberman;George Dl;M. Oren
p53肿瘤抑制基因产物可与mdm2推定原基因编码的多肽复合。此外，mdm2 mRNA水平已显示在野生型（wt）p53活化后增加。为了确定野生型p53对mdm2 mRNA的影响的基础，我们研究了mdm2基因与p53的相互作用。我们报告，野生型p53可以结合序列特异性的DNA区域位于下游的mdm2基因的外显子1。这与显著的p53依赖性转录激活相关。有效的p53依赖的反式激活可以用缺少推定的mdm2启动子的mdm2基因组DNA片段获得。这些发现表明，p53可以诱导转录从一个内部启动子位于mdm2基因。这些发现提出了这样的可能性，除了增加mdm2 mRNA的总体水平，野生型p53也可能调节mdm2转录本的库存在于细胞内。
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.