Census and evaluation of p53 target genes

By Martin Fischer. Oncogene, 2017

848 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/2f6fe4db47e008bb1c6528c0265ad81e68f9555f

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In Molecular Biology

1. John N. Weinstein
2. T. Soussi
3. Kurt Engeland
4. Olivier Lichtarge

In Oncology

1. John N. Weinstein
2. T. Soussi
3. Kurt Engeland
4. Olivier Lichtarge

Citations in the corpus

• Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas (2018, neutral): “For example, frequent TP53 somatic mutations in many cancer types can disrupt the DNA damage response, apoptosis, or senescence pathways active in many early-stage cancers (Bartkova et al., 2005; Fischer, 2017; Gorgoulis et al., 2005; Pfister and Prives, 2017).”
• Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas (2019, background): “…of genes, target specificity depending on cell type and context as well as the nature and intensity of the cell stressor (el-Deiry et al., 1993; Fischer, 2017; Mello and Attardi, 2017; Vousden and Prives, 2009). p53 upregulates genes that encode cell cycle inhibitors, apoptosis inducers, DNA…”
• Cell cycle regulation: p53-p21-RB signaling (2022, background): “p53 is a transcription factor that activates a large number of genes [31, 32].”