Evidence map›Paper›PMID 33444431›Full record

ArticleNucleic acids research2021

The complex architecture of p53 binding sites.

Alon Senitzki, Jessy Safieh, Vasundhara Sharma, Dmitrij Golovenko, Yael Danin-Poleg, Alberto Inga, Tali E Haran

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. iScience · 2024
    Article
  5. Review
  6. Review
  7. Context dependent activity of p63-bound gene regulatory elements.bioRxiv : the preprint server for biology · 2024
    Article
  8. Article
  9. A molecular mechanism for the "digital" response of p53 to stress.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Structural Basis of Mutation-Dependent p53 Tetramerization Deficiency.International journal of molecular sciences · 2022
    Article
  14. Review
  15. Article
  16. 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

7 authors at 2 institutions in 2 countries.

Alon SenitzkiDepartment of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 3200003, Israel.
Jessy SafiehDepartment of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 3200003, Israel.
Vasundhara SharmaDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Trento, TN, Italy.
Dmitrij GolovenkoDepartment of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 3200003, Israel.
Yael Danin-PolegDepartment of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 3200003, Israel.
Alberto IngaDepartment of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Trento, TN, Italy.
Tali E HaranDepartment of Biology, Technion - Israel Institute of Technology, Technion City, Haifa 3200003, Israel.
Technion – Israel Institute of Technology · ILUniversity of Trento · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sequence-specific protein-DNA interactions are at the heart of the response of the tumor-suppressor p53 to numerous physiological and stress-related signals. Large variability has been previously reported in p53 binding to and transactivating from p53 response elements (REs) due, at least in part, to changes in direct (base) and indirect (shape) readouts of p53 REs. Here, we dissect p53 REs to decipher the mechanism by which p53 optimizes this highly regulated variable level of interaction with its DNA binding sites. We show that hemi-specific binding is more prevalent in p53 REs than previously envisioned. We reveal that sequences flanking the REs modulate p53 binding and activity and show that these effects extend to 4-5 bp from the REs. Moreover, we show here that the arrangement of p53 half-sites within its REs, relative to transcription direction, has been fine-tuned by selection pressure to optimize and regulate the response levels from p53 REs. This directionality in the REs arrangement is at least partly encoded in the structural properties of the REs. Furthermore, we show here that in the p21-5' RE the orientation of the half-sites is such that the effect of the flanking sequences is minimized and we discuss its advantages.

Indexed as

Response ElementsTranscriptional ActivationBinding SitesDNAHumansNucleic Acid ConformationProtein BindingTumor Suppressor Protein p53Up-RegulationDNATP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID33444431
PMCPMC7897521
OpenAlexW3120613617

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

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.