ArticleProceedings of the National Academy of Sciences of the United States of America2008
Functional evolution of the p53 regulatory network through its target response elements.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Conservation and divergence of the p53 gene regulatory network between mice and humans.Oncogene · 2019Pooled it
- The TP53 tumor suppressor gene: From molecular biology to clinical investigations.Journal of internal medicine · 2025Review
- p53motifDB: integration of genomic information and tumour suppressor p53 binding motifs.Database : the journal of biological databases and curation · 2025Article
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- The complex architecture of p53 binding sites.Nucleic acids research · 2021Article
- Tumor suppressor p53: from engaging DNA to target gene regulation.Nucleic acids research · 2020Article
- Regulating tumor suppressor genes: post-translational modifications.Signal transduction and targeted therapy · 2020Review
- A Protein in the YeastBiomolecules · 2020Article
- Discordant gene responses to radiation in humans and mice and the role of hematopoietically humanized mice in the search for radiation biomarkers.Scientific reports · 2019Article
- Shaping the regulation of the p53 mRNA tumour suppressor: the co-evolution of genetic signatures.BMC cancer · 2019Review
- The p53 mRNA: an integral part of the cellular stress response.Nucleic acids research · 2019Review
- DNA Damage Response and Repair, DNA Methylation, and Cell Death in Human Neurons and Experimental Animal Neurons Are Different.Journal of neuropathology and experimental neurology · 2018Article
- A highly specific SpCas9 variant is identified by in vivo screening in yeast.Nature biotechnology · 2018Article
- Conservation and Divergence of p53 Oscillation Dynamics across Species.Cell systems · 2017Article
- Identification of p53-target genes in Danio rerio.Scientific reports · 2016Article
- The DNA damage-induced cell death response: a roadmap to kill cancer cells.Cellular and molecular life sciences : CMLS · 2016Review
- Two p53 tetramers bind one consensus DNA response element.Nucleic acids research · 2016Article
- TLR2∆22 (-196-174) significantly increases the risk of breast cancer in females carrying proline allele at codon 72 of TP53 gene: a case-control study from four ethnic groups of North Eastern region of India.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Whole-genome cartography of p53 response elements ranked on transactivation potential.BMC genomics · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Transcriptional network evolution is central to the development of complex biological systems. Networks can evolve through variation of master regulators and/or by changes in regulation of genes within networks. To gain insight into meaningful evolutionary differences in large networks, it is essential to address the functional consequences of sequence differences in response elements (REs) targeted by transcription factors. Using a combination of custom bioinformatics and multispecies alignment of promoter regions, we investigated the functional evolution of REs in terms of responsiveness to the sequence-specific transcription factor p53, a tumor suppressor and master regulator of stress responses. We identified REs orthologous to known p53 targets in human and rodent cells or alternatively REs related to the established p53 consensus. The orthologous REs were assigned p53 transactivation capabilities based on rules determined from model systems, and a functional heat map was developed to visually summarize conservation of sequence and relative level of responsiveness to p53 for 47 REs in 14 species. Individual REs exhibited marked differences in transactivation potentials and widespread evolutionary turnover. Functional differences were often not predicted from consensus sequence evaluations. Of the established human p53 REs analyzed, 91% had sequence conservation in at least one nonprimate species compared with 67.5% for functional conservation. Surprisingly, there was almost no conservation of functional REs for genes involved in DNA metabolism or repair between humans and rodents, suggesting important differences in p53 stress responses and cancer development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.