Census and evaluation of p53 target genes.
Census and evaluation of p53 target genes.
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DOI：
10.1038/onc.2016.502
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发表时间：
2017-07-13
期刊：
影响因子：
8
通讯作者：
Fischer M
中科院分区：
文献类型：
--
作者：
Fischer M
肿瘤抑制因子p53主要作为转录因子发挥作用。TP53基因的突变改变了其反应途径，是许多癌症发展的核心。大量赋予p53肿瘤抑制功能的p53靶基因的发现，导致了越来越复杂的p53功能模型。然而，最近的荟萃分析方法简化了我们对p53作为转录因子如何发挥作用的理解。在这里介绍的调查中，总共确定了3661个直接p53靶基因，其中包括来自13个高通量研究的3509个潜在靶基因和来自单个基因分析的346个靶基因。在个别研究中报告的p53靶基因与13个高通量研究中确定的靶基因的比较显示出有限的一致性。在此，基于荟萃分析数据对p53靶基因进行了评估，结果显示高置信度的p53靶基因参与多种细胞反应，包括细胞周期阻滞、DNA修复、凋亡、代谢、自噬、mRNA翻译和反馈机制。然而，许多p53靶基因仅在少数研究中被鉴定，并且具有较高的假阳性可能性。虽然已经提出了许多机制介导的基因调控响应p53，在我们的理解p53功能的最新进展表明，p53本身是唯一的转录激活因子，基因下调p53是间接的，需要p21。考虑到p53作为转录激活因子的功能，最近的研究结果指出了一种简单的调控手段。
The tumor suppressor p53 functions primarily as a transcription factor. Mutation of the TP53 gene alters its response pathway, and is central to the development of many cancers. The discovery of a large number of p53 target genes, which confer p53’s tumor suppressor function, has led to increasingly complex models of p53 function. Recent meta-analysis approaches, however, are simplifying our understanding of how p53 functions as a transcription factor. In the survey presented here, a total set of 3661 direct p53 target genes is identified that comprise 3509 potential targets from 13 high-throughput studies, and 346 target genes from individual gene analyses. Comparison of the p53 target genes reported in individual studies with those identified in 13 high-throughput studies reveals limited consistency. Here, p53 target genes have been evaluated based on the meta-analysis data, and the results show that high-confidence p53 target genes are involved in multiple cellular responses, including cell cycle arrest, DNA repair, apoptosis, metabolism, autophagy, mRNA translation and feedback mechanisms. However, many p53 target genes are identified only in a small number of studies and have a higher likelihood of being false positives. While numerous mechanisms have been proposed for mediating gene regulation in response to p53, recent advances in our understanding of p53 function show that p53 itself is solely an activator of transcription, and gene downregulation by p53 is indirect and requires p21. Taking into account the function of p53 as an activator of transcription, recent results point to an unsophisticated means of regulation.
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影响因子：
3.7
作者：
Azzam G;Wang X;Bell D;Murphy ME
通讯作者：
Murphy ME
影响因子：
14.9
作者：
Böhlig L;Friedrich M;Engeland K
通讯作者：
Engeland K
DOI：
10.1073/pnas.202485699
发表时间：
2002-10-01
影响因子：
11.1
作者：
Adimoolam, S;Ford, JM
通讯作者：
Ford, JM
影响因子：
64.8
作者：
BRUGAROLAS, J;CHANDRASEKARAN, C;HANNON, GJ
通讯作者：
HANNON, GJ
DNA损伤通过直接结合其启动子引起染色质重塑，从而诱导p53降低CDC20。
影响因子：
14.9
作者：
Banerjee T;Nath S;Roychoudhury S
通讯作者：
Roychoudhury S