The transcription factor p53: not a repressor, solely an activator.
The transcription factor p53: not a repressor, solely an activator.
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DOI：
10.4161/15384101.2014.949083
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Engeland K
中科院分区：
文献类型：
--
作者：
Fischer M;Steiner L;Engeland K
肿瘤抑制因子p53的主要功能是转录调节。通常认为p53依赖性转录激活通过结合靶基因启动子中的特异性识别位点而发生。此外，已经假设了几种p53依赖性转录抑制的模型。在这里，我们基于全基因组数据的计算荟萃分析来评估这些模型。令人惊讶的是，p53依赖性基因调控的几个主要模型是不可信的。大规模数据的荟萃分析无法证实直接阻遏的p53靶基因的报道，并伪造了直接阻遏的模型。这一观点得到了对被p53直接抑制的代表性基因的实验再分析的支持。因此，p53不是转录的直接阻遏物，而是单独激活其靶基因。此外，基于p53与激活转录因子的干扰的模型以及基于ncRNA功能的模型也不受荟萃分析的支持。作为直接抑制模型的替代，荟萃分析得出的结论是，p53通过激活p53-p21-DREAM/RB通路间接抑制转录。
The predominant function of the tumor suppressor p53 is transcriptional regulation. It is generally accepted that p53-dependent transcriptional activation occurs by binding to a specific recognition site in promoters of target genes. Additionally, several models for p53-dependent transcriptional repression have been postulated. Here, we evaluate these models based on a computational meta-analysis of genome-wide data. Surprisingly, several major models of p53-dependent gene regulation are implausible. Meta-analysis of large-scale data is unable to confirm reports on directly repressed p53 target genes and falsifies models of direct repression. This notion is supported by experimental re-analysis of representative genes reported as directly repressed by p53. Therefore, p53 is not a direct repressor of transcription, but solely activates its target genes. Moreover, models based on interference of p53 with activating transcription factors as well as models based on the function of ncRNAs are also not supported by the meta-analysis. As an alternative to models of direct repression, the meta-analysis leads to the conclusion that p53 represses transcription indirectly by activation of the p53-p21-DREAM/RB pathway.