ArticlePLoS genetics2008
Noncanonical DNA motifs as transactivation targets by wild type and mutant p53.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 71 papers.
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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
71 citing papers in PubMed, 101 citations in OpenAlex.
- Altered-function p53 missense mutations identified in breast cancers can have subtle effects on transactivation.Molecular cancer research : MCR · 2010Trial
- Determinants of p53 DNA binding, gene regulation, and cell fate decisions.Cell death and differentiation · 2024Review
- Optimisation of TP53 reporters by systematic dissection of synthetic TP53 response elements.Nucleic acids research · 2023Article
- Sequence Properties of An Intramolecular Interaction That Inhibits p53 DNA Binding.Biomolecules · 2022Article
- TP53-inducible putative long noncoding RNAs encode functional polypeptides that suppress cell proliferation.Genome research · 2022Article
- Article
- P53 protein and the diseases in central nervous system.Frontiers in genetics · 2022Review
- Tumor suppressor p53: Biology, signaling pathways, and therapeutic targeting.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Structural and Drug Targeting Insights on Mutant p53.Cancers · 2021Review
- The complex architecture of p53 binding sites.Nucleic acids research · 2021Article
- Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis.Cancers · 2020Review
- A Protein in the YeastBiomolecules · 2020Article
- The Influence of Quadruplex Structure in Proximity to P53 Target Sequences on the Transactivation Potential of P53 Alpha Isoforms.International journal of molecular sciences · 2019Article
- Roles of p53 Family Structure and Function in Non-Canonical Response Element Binding and Activation.International journal of molecular sciences · 2019Review
- Expression of Micro-RNA-492 (MiR-492) in Human Cervical Cancer Cell Lines is Upregulated by Transfection with Wild-Type P53, Irradiation, and 5-Fluorouracil Treatment In Vitro.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Diverse p53/DNA binding modes expand the repertoire of p53 response elements.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Census and evaluation of p53 target genes.Oncogene · 2017Review
- Recognition of Local DNA Structures by p53 Protein.International journal of molecular sciences · 2017Review
- Two p53 tetramers bind one consensus DNA response element.Nucleic acids research · 2016Article
- A/T gap tolerance in the core sequence and flanking sequence requirements of non-canonical p53 response elements.Journal of biochemistry · 2016Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedNourredine, Maher [corrected to Noureddine, Maher]; Bell, Douglas [corrected to Bell, Douglas A]
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites separated by 0-13 nucleotides (nt), originally defined by the consensus RRRCWWGYYY (n = 0-13) RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs) by wild type (WT) and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi-in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical (1/2)-(a single decamer) and (3/4)-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of (1/2)- and (3/4)-site REs greatly expands the p53 master regulatory network.
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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.