Evidence map›Paper›PMID 12923058›Full record

ArticleGenes & development2003

Identification of a DNA-binding site and transcriptional target for the EWS-WT1(+KTS) oncoprotein.

Paul A Reynolds, Gromoslaw A Smolen, Rachel E Palmer, Dennis Sgroi, Vijay Yajnik, William L Gerald, Daniel A Haber

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
–field-weighted citation impact
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

25 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
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  4. Article
  5. Small round cell sarcomas.Nature reviews. Disease primers · 2022
    Review
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  18. Proteomic analysis of human nail plate.Journal of proteome research · 2010
    Article
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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 3 institutions in 1 country.

Paul A ReynoldsMassachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, MA 02129, USA.
Gromoslaw A Smolen
Rachel E Palmer
Dennis Sgroi
Vijay Yajnik
William L Gerald
Daniel A Haber
Massachusetts General Hospital · USHarvard University · USMemorial Sloan Kettering Cancer Center · US

Funding

Targets of Ewing Sarcoma-Wilms Tumor 1 OncoproteinR01CA090627 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI HABER, DANIEL A. · 2002 to 2006
$1.3M
NCI NIH HHS CA 90627NCI NIH HHS R01 CA090627
6 · The paper itself

Abstract

Desmoplastic small round cell tumor (DSRCT) is defined by a chimeric transcription factor, resulting from fusion of the N-terminal domain of the Ewing's sarcoma gene EWS to the three C-terminal zinc fingers of the Wilms' tumor suppressor WT1. Although DNA-binding sites have been defined for the uninterrupted WT1 zinc finger domains, the most prevalent isoforms of both WT1 and EWS-WT1 have an insertion of three amino acids [lysine, threonine, and serine (KTS)], which abrogates binding to known consensus sequences and transactivation of known target genes. Here, we used cDNA subtractive hybridization to identify an endogenous gene, LRRC15, which is specifically up-regulated after inducible expression of EWS-WT1(+KTS) in cancer cell lines, and is expressed within primary DSRCT cells. The chimeric protein binds in vitro and in vivo to a specific element upstream of LRRC15, leading to dramatic transcriptional activation. Mutagenesis studies define the optimal binding site of the (+KTS) isoform of EWS-WT1 as 5'-GGAGG(A/G)-3'. LRRC15 encodes a leucine-rich transmembrane protein, present at the leading edge of migrating cells, the expression of which in normal tissues is restricted to the invasive cytotrophoblast layer of the placenta; small interfering (siRNA)-mediated suppression of LRRC15 expression in breast cancer cells leads to abrogation of invasiveness in vitro. Together, these observations define the consequence of (KTS) insertion within WT1-derived zinc fingers, and identify a novel EWS-WT1 transcriptional target implicated in tumor invasiveness.

Indexed as

Amino Acid SequenceBinding SitesDNAHumansMolecular Sequence DataOncogene Proteins, FusionPeritoneal NeoplasmsRNA Processing, Post-TranscriptionalDNAEWS1-WT1 fusion protein, humanOncogene Proteins, Fusion

Identifiers

PMID12923058
PMCPMC196452
OpenAlexW2109193519

What OpenQuestion holds

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Registered trials

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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.