Evidence map›Paper›PMID 21859680›Full record

ArticleJournal of biomolecular screening2011

A biochemical screen for identification of small-molecule regulators of the Wnt pathway using Xenopus egg extracts.

Curtis A Thorne, Bonnie Lafleur, Michelle Lewis, Alison J Hanson, Kristin K Jernigan, David C Weaver, Kari A Huppert, Tony W Chen, Chonlarat Wichaidit, Christopher S Cselenyi and 9 more

Abstract read
In one paragraph

Article in Journal of biomolecular screening, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Feedback in the β-catenin destruction complex imparts bistability and cellular memory.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  2. Chemical Screening Using Cell-FreeCold Spring Harbor protocols · 2018
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Small-molecule high-throughput screening utilizing Xenopus egg extract.Methods in molecular biology (Clifton, N.J.) · 2015
    Article
  8. Article
  9. Reconstitution Of β-catenin degradation in Xenopus egg extract.Journal of visualized experiments : JoVE · 2014
    Article
  10. 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

19 authors.

Curtis A ThorneDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-8240, USA.
Bonnie Lafleur
Michelle Lewis
Alison J Hanson
Kristin K Jernigan
David C Weaver
Kari A Huppert
Tony W Chen
Chonlarat Wichaidit
Christopher S Cselenyi
Emilios Tahinci
Kelly C Meyers
Emily Waskow
Darren Orton
Adrian Salic
Laura A Lee
David J Robbins
Stacey S Huppert
Ethan Lee

Funding

Understanding and Controlling p120 Dysfunction in CRCP50CA095103 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI COFFEY, ROBERT J. · 2002 to 2017
$33.6M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007347 · NIGMS · VANDERBILT UNIVERSITY · PI WILLIAMS, CHRISTOPHER S. · 1985 to 2023
$26.3M
MULTIDISCIPLINARY TRAINING IN MOLECULAR ENDOCRINOLOGYT32DK007563 · NIDDK · VANDERBILT UNIVERSITY · PI Richard M O'Brien · 1988 to 2026
$15.9M
MULTIDISCIPLINARY BASIC RESEARCH TRAINING IN CANCERT32CA009592 · NCI · VANDERBILT UNIVERSITY · PI Justin M Balko, Julie A Rhoades (Sterling) · 1987 to 2026
$10.4M
Regulation of beta-catenin degradation during Wnt signal transductionR01GM081635 · NIGMS · VANDERBILT UNIVERSITY · PI LEE, ETHAN · 2007 to 2016
$2.4M
Turnkey solution for image phenotype classificationR01GM085442 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI ALTSCHULER, STEVEN J · 2008 to 2011
$1.2M
NCI NIH HHS P50 CA095103NCI NIH HHS P50 CA95103NCI NIH HHS T32 CA009592NCI NIH HHS T32 CA09592NIDDK NIH HHS 5 T 32 DK007563NIDDK NIH HHS T32 DK007563NIGMS NIH HHS 1 R01 GM081635-01NIGMS NIH HHS 5 T32 GM007347NIGMS NIH HHS GM085442NIGMS NIH HHS R01 GM081635NIGMS NIH HHS R01 GM085442NIGMS NIH HHS T32 GM007347
6 · The paper itself

Abstract

Misregulation of the Wnt pathway has been shown to be responsible for a variety of human diseases, most notably cancers. Screens for inhibitors of this pathway have been performed almost exclusively using cultured mammalian cells or with purified proteins. We have previously developed a biochemical assay using Xenopus egg extracts to recapitulate key cytoplasmic events in the Wnt pathway. Using this biochemical system, we show that a recombinant form of the Wnt coreceptor, LRP6, regulates the stability of two key components of the Wnt pathway (β-catenin and Axin) in opposing fashion. We have now fused β-catenin and Axin to firefly and Renilla luciferase, respectively, and demonstrate that the fusion proteins behave similarly as their wild-type counterparts. Using this dual luciferase readout, we adapted the Xenopus extracts system for high-throughput screening. Results from these screens demonstrate signal distribution curves that reflect the complexity of the library screened. Of several compounds identified as cytoplasmic modulators of the Wnt pathway, one was further validated as a bona fide inhibitor of the Wnt pathway in cultured mammalian cells and Xenopus embryos. We show that other embryonic pathways may be amendable to screening for inhibitors/modulators in Xenopus egg extracts.

Indexed as

High-Throughput Screening AssaysSmall Molecule LibrariesAnimalsAxin Proteinbeta CateninEnzyme AssaysFlavonesHEK293 CellsHeLa CellsHumansLuciferasesReproducibility of ResultsWnt Signaling PathwayXenopus laevisAxin Proteinbeta CateninFlavonesLuciferasesSmall Molecule Libraries

Identifiers

PMID21859680
PMCPMC3694444

What OpenQuestion holds

Textmetadata
LicenceTDM
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.