Census and evaluation of p53 target genes

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...

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Vydané v:	Oncogene Ročník 36; číslo 28; s. 3943 - 3956
Hlavný autor:	Fischer, M
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 13.07.2017 Nature Publishing Group
Predmet:	38/47 45/47 631/337/572 631/80/82 Analysis Animals Apoptosis Cancer Cell Biology Cell cycle Census Data processing DNA repair Feedback Gene Expression Profiling - statistics & numerical data Gene Expression Regulation Gene regulation Gene targeting Genes Genetic Association Studies - statistics & numerical data Genetic regulation GTP-binding protein Health aspects High-Throughput Screening Assays - statistics & numerical data Human Genetics Humans Internal Medicine Medicine Medicine & Public Health Meta-Analysis as Topic Mutation Oncology p53 Protein Phagocytosis Promoters (Genetics) Properties Review Transcription factors Tumor suppressor genes Tumor Suppressor Protein p53 - physiology
ISSN:	0950-9232, 1476-5594, 1476-5594
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	0950-9232 1476-5594 1476-5594
DOI:	10.1038/onc.2016.502