Transcriptional Regulation by p53
Transcriptional Regulation by p53
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DOI：
10.1101/cshperspect.a000935
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发表时间：
2010-08-01
影响因子：
7.2
通讯作者：
Prives, Carol
中科院分区：
文献类型：
--
作者：
Beckerman, Rachel;Prives, Carol
p53的失活对于大多数肿瘤的形成至关重要。因此，阐明p53蛋白在保护细胞免于癌变中的关键功能是一个有价值的目标。可以说，p53最重要的功能是作为一种转录因子，直接调节细胞的RNA聚合酶II（RNAP II）转录的基因中的数百个，并间接调节数千个其他基因。事实上，p53是研究最充分的哺乳动物转录因子。p53四聚体与其反应元件结合，在反应元件中，p53四聚体可以募集不同的转录辅助调节因子，如组蛋白修饰酶、染色质重塑因子、介体复合物的亚基以及一般转录机制和前起始复合物（PIC）的组分，以调节靶基因座处的RNAPII活性（Laptenko and Prives 2006）。p53转录程序以刺激特异性方式调节（Murray-Zmijewski等人，2008; Vousden和Prives 2009），从而响应不同的p53激活剂诱导不同的p53靶基因子集，这可能允许细胞调整其对不同类型的应激的反应。p53如何能够区分这些不同的基因座是深入研究的主题。在这里，我们描述了p53介导的转录调控和靶基因启动子选择性的基本原理的关键方面。
Inactivation of p53 is critical for the formation of most tumors. Illumination of the key function(s) of p53 protein in protecting cells from becoming cancerous is therefore a worthy goal. Arguably p53's most important function is to act as a transcription factor that directly regulates perhaps several hundred of the cell's RNA polymerase II (RNAP II)-transcribed genes, and indirectly regulates thousands of others. Indeed p53 is the most well studied mammalian transcription factor. The p53 tetramer binds to its response element where it can recruit diverse transcriptional coregulators such as histone modifying enzymes, chromatin remodeling factors, subunits of the mediator complex, and components of general transcription machinery and preinitiation complex (PIC) to modulate RNAPII activity at target loci (Laptenko and Prives 2006). The p53 transcriptional program is regulated in a stimulus-specific fashion (Murray-Zmijewski et al. 2008; Vousden and Prives 2009), whereby distinct subsets of p53 target genes are induced in response to different p53-activating agents, likely allowing cells to tailor their response to different types of stress. How p53 is able to discriminate between these different loci is the subject of intense research. Here, we describe key aspects of the fundamentals of p53-mediated transcriptional regulation and target gene promoter selectivity.