Evidence map›Paper›PMID 17420471›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2007

A mechanism for transcriptional repression dependent on the BRCA1 E3 ubiquitin ligase.

Andrew A Horwitz, El Bachir Affar, George F Heine, Yang Shi, Jeffrey D Parvin

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. 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
2.8field-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

24 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Journal of Cancer · 2019
    Review
  6. Review
  7. Article
  8. Dysregulation of ubiquitin ligases in cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2015
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. BRCA1, hormone, and tissue-specific tumor suppression.International journal of biological sciences · 2009
    Review
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 2 institutions in 1 country.

Andrew A HorwitzDepartment of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
El Bachir Affar
George F Heine
Yang Shi
Jeffrey D Parvin
Salk Institute for Biological Studies · USBrigham and Women's Hospital · US

Funding

BRCA1 FunctionR01CA090281 · NCI · OHIO STATE UNIVERSITY · PI PARVIN, JEFFREY D · 2002 to 2006
$1.7M
NCI NIH HHS CA90281NCI NIH HHS R01 CA090281
6 · The paper itself

Abstract

Loss of function of the tumor suppressor protein BRCA1 is responsible for a high percentage of familial and also sporadic breast cancers. Early work identified a stimulatory transcriptional coactivator function for the BRCA1 protein, and more recently, BRCA1 has been implicated in transcriptional repression, although few examples of repressed genes have been characterized. We recently used an in vitro transcription assay to identify a biochemical mechanism that explained the BRCA1 stimulatory activity. In this study, we identified an ubiquitin-dependent mechanism by which BRCA1 inhibits transcription. BRCA1 ubiquitinates the transcriptional preinitiation complex, preventing stable association of TFIIE and TFIIH, and thus blocks the initiation of mRNA synthesis. What is striking about this mechanism of regulation by BRCA1 is that the ubiquitination of the preinitiation complex is not targeting proteins for degradation by the proteasome, nor are ubiquitin receptors modifying the activity, but rather the ubiquitin moiety itself interferes with the assembly of basal transcription factors at the promoter. Using RNAi to knockdown expression of the endogenous BRCA1 protein, we assessed the level of repression dependent on BRCA1 in the cell, and we found that BRCA1 is at least as significant a transcriptional repressor as it is an activator. These results define a biochemical mechanism by which the BRCA1 enzymatic activity regulates a key cellular process.

Indexed as

BRCA1 ProteinGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHeLa CellsHumansPromoter Regions, GeneticRepressor ProteinsTranscription FactorsUbiquitinUbiquitin-Protein LigasesBRCA1 ProteinRepressor ProteinsTranscription FactorsUbiquitinUbiquitin-Protein Ligases

Identifiers

PMID17420471
PMCPMC1871834
OpenAlexW2064633787

What OpenQuestion holds

Textmetadata
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.