Evidence map›Paper›PMID 20585628›Full record

ArticlePLoS genetics2010

Tandem E2F binding sites in the promoter of the p107 cell cycle regulator control p107 expression and its cellular functions.

Deborah L Burkhart, Stacey E Wirt, Anne-Flore Zmoos, Michael S Kareta, Julien Sage

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

24 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. E2F regulation of theProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Molecular cancer research : MCR · 2021
    Article
  9. Article
  10. Article
  11. The Temporal Regulation of S Phase Proteins During GAdvances in experimental medicine and biology · 2017
    Review
  12. Cell Death in Chondrocytes, Osteoblasts, and Osteocytes.International journal of molecular sciences · 2016
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

5 authors at 3 institutions in 1 country.

Deborah L BurkhartDepartments of Pediatrics and Genetics, Stanford Medical School, Stanford, California, United States of America.
Stacey E Wirt
Anne-Flore Zmoos
Michael S Kareta
Julien Sage
California Institute for Regenerative Medicine · USStanford Medicine · USPediatrics and Genetics · US

Funding

Leveraging innovative technologies in basic and clinical cancer researchT32CA009302 · NCI · STANFORD UNIVERSITY · PI LAURA D ATTARDI, Aaron M Newman · 1985 to 2026
$19.1M
TUMOR BIOLOGYT32CA009151 · NCI · STANFORD UNIVERSITY · PI CLEARY, MICHAEL L · 1985 to 2014
$5.5M
NCI NIH HHS T32 CA009151NCI NIH HHS T32 CA009302
6 · The paper itself

Abstract

The retinoblastoma tumor suppressor (Rb) is a potent and ubiquitously expressed cell cycle regulator, but patients with a germline Rb mutation develop a very specific tumor spectrum. This surprising observation raises the possibility that mechanisms that compensate for loss of Rb function are present or activated in many cell types. In particular, p107, a protein related to Rb, has been shown to functionally overlap for loss of Rb in several cellular contexts. To investigate the mechanisms underlying this functional redundancy between Rb and p107 in vivo, we used gene targeting in embryonic stem cells to engineer point mutations in two consensus E2F binding sites in the endogenous p107 promoter. Analysis of normal and mutant cells by gene expression and chromatin immunoprecipitation assays showed that members of the Rb and E2F families directly bound these two sites. Furthermore, we found that these two E2F sites controlled both the repression of p107 in quiescent cells and also its activation in cycling cells, as well as in Rb mutant cells. Cell cycle assays further indicated that activation of p107 transcription during S phase through the two E2F binding sites was critical for controlled cell cycle progression, uncovering a specific role for p107 to slow proliferation in mammalian cells. Direct transcriptional repression of p107 by Rb and E2F family members provides a molecular mechanism for a critical negative feedback loop during cell cycle progression and tumorigenesis. These experiments also suggest novel therapeutic strategies to increase the p107 levels in tumor cells.

Indexed as

Cell CyclePromoter Regions, GeneticAnimalsBase SequenceBinding SitesCell Cycle ProteinsCells, CulturedConserved SequenceE2F Transcription FactorsHumansMiceMolecular Sequence DataRetinoblastoma-Like Protein p107Sequence AlignmentTranscription, GeneticCell Cycle ProteinsE2F Transcription FactorsRbl1 protein, mouseRetinoblastoma-Like Protein p107

Identifiers

PMID20585628
PMCPMC2891812
OpenAlexW2056305752

What OpenQuestion holds

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LicenceCC BY
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.