Evidence map›Paper›PMID 27034469›Full record

ArticleNucleic acids research2016

Two p53 tetramers bind one consensus DNA response element.

Sinéad Kearns, Rudi Lurz, Elena V Orlova, Andrei L Okorokov

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 37 citations in OpenAlex.

  1. Review
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  5. Review
  6. FOXO4 interacts with p53 TAD and CRD and inhibits its binding to DNA.Protein science : a publication of the Protein Society · 2022
    Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. How p53 Molecules Solve the Target DNA Search Problem: A Review.International journal of molecular sciences · 2020
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
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  18. Article
  19. 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 · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 2 countries.

Sinéad KearnsInstitute for Structural and Molecular Biology, School of Biological Sciences, Birkbeck College, London WC1E 7HX, UK Wolfson Institute for Biomedical Research, Division of Medicine, University College London, London WC1E 6BT, UK.
Rudi LurzMax Planck Institute for Molecular Genetics, Ihnestrasse, Berlin 14195, Germany.
Elena V OrlovaInstitute for Structural and Molecular Biology, School of Biological Sciences, Birkbeck College, London WC1E 7HX, UK e.orlova@cryst.bbk.ac.uk.
Andrei L OkorokovWolfson Institute for Biomedical Research, Division of Medicine, University College London, London WC1E 6BT, UK a.okorokov@ucl.ac.uk.
Birkbeck, University of London · GBMax Planck Institute for Molecular Genetics · DEUniversity College London · GB

Funding

Biotechnology and Biological Sciences Research Council BB/E019862/1Biotechnology and Biological Sciences Research Council BB/E021042/1
6 · The paper itself

Abstract

p53 tumor suppressor is a transcription factor that controls cell cycle and genetic integrity. In response to genotoxic stress p53 activates DNA repair, cell cycle arrest, apoptosis or senescence, which are initiated via p53 binding to its specific DNA response elements (RE). The consensus p53 DNA RE consists of two decameric palindromic half-site sequences. Crystallographic studies have demonstrated that two isolated p53 DNA-binding core domains interact with one half-site of the p53 DNA REs suggesting that one p53 tetramer is bound to one RE. However, our recent 3D cryo-EM studies showed that the full-length p53 tetramer is bound to only one half-site of RE.Here, we have used biochemical and electron microscopy (EM) methods to analyze DNA-binding of human and murine p53 tetramers to various p53 DNA REs. Our new results demonstrate that two p53 tetramers can interact sequence-specifically with one DNA RE at the same time. In particular, the EM structural analysis revealed that two p53 tetramers bind one DNA RE simultaneously with DNA positioned between them. These results demonstrate a mode different from that assumed previously for the p53-DNA interaction and suggest important biological implications on p53 activity as a transcriptional regulator of cellular response to stress.

Indexed as

AnimalsBinding SitesCell CycleDNA-Binding ProteinsDNA DamageHumansInverted Repeat SequencesMiceProtein ConformationProtein DomainsProtein MultimerizationProtein Structure, TertiaryResponse ElementsTranscriptional ActivationTumor Suppressor Protein p53DNA-Binding ProteinsTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID27034469
PMCPMC5291249
OpenAlexW2330738817

What OpenQuestion holds

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Registered trials

None linked

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.