THE P53 MDM-2 AUTOREGULATORY FEEDBACK LOOP
THE P53 MDM-2 AUTOREGULATORY FEEDBACK LOOP
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DOI：
10.1101/gad.7.7a.1126
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发表时间：
1993-07-01
影响因子：
10.5
通讯作者：
LEVINE, AJ
中科院分区：
文献类型：
--
作者：
WU, XW;BAYLE, JH;LEVINE, AJ
P53蛋白可以结合一组特定的DNA序列，这可能会激活与这些DNA元件相邻的基因的转录。MDM-2基因含有一个P53 DNA结合位点和一个遗传反应元件，因此MDM-2基因的表达可以由野生型P53蛋白的水平来调节。反过来，MDM-2蛋白可以与p53复合，降低其在MDM-2基因反应元件上作为正转录因子的能力。通过这种方式，MDM-2基因被自动调节。P53蛋白在转录水平上调节MDM-2基因，MDM-2蛋白在其活性水平上调节P53蛋白。这就产生了一个反馈环，既调节P53蛋白的活性，又调节MDM-2基因的表达。
The p53 protein can bind to a set of specific DNA sequences, and this may activate the transcription of genes adjacent to these DNA elements. The mdm-2 gene is shown here to contain a p53 DNA-binding site and a genetically responsive element such that expression of the mdm-2 gene can be regulated by the level of wild-type p53 protein. The mdm-2 protein, in turn, can complex with p53 and decrease its ability to act as a positive transcription factor at the mdm-2 gene-responsive element. In this way, the mdm-2 gene is autoregulated. The p53 protein regulates the mdm-2 gene at the level of transcription, and the mdm-2 protein regulates the p53 protein at the level of its activity. This creates a feedback loop that regulates both the activity of the p53 protein and the expression of the mdm-2 gene.