Evidence map›Paper›PMID 27852897›Full record

ArticleMolecular biology of the cell2017

Reconstituting regulation of the canonical Wnt pathway by engineering a minimal β-catenin destruction machine.

Mira I Pronobis, Natalie Deuitch, Vinya Posham, Yuko Mimori-Kiyosue, Mark Peifer

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

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  16. Mechanisms of Wnt signaling and control.Wiley interdisciplinary reviews. Systems biology and medicine · 2018
    Review
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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

5 authors at 1 institution in 1 country.

Mira I PronobisCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Natalie DeuitchDepartment of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Vinya PoshamDepartment of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Yuko Mimori-KiyosueCellular Dynamics Analysis Unit, RIKEN Center for Life Science Technologies, Kobe 650-0047, Japan.
Mark PeiferCurriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 peifer@unc.edu.
University of North Carolina at Chapel Hill · US

Funding

Regulating cell fate and shaping the body plan during morphogenesis and their alteration during oncogenesisR35GM118096 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Mark A. Peifer · 2016 to 2026
$6.5M
A model system to study the tumor suppressor APCR01GM067236 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEIFER, MARK A. · 2002 to 2015
$2.8M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM067236NIGMS NIH HHS R35 GM118096
6 · The paper itself

Abstract

Negatively regulating key signaling pathways is critical to development and altered in cancer. Wnt signaling is kept off by the destruction complex, which is assembled around the tumor suppressors APC and Axin and targets β-catenin for destruction. Axin and APC are large proteins with many domains and motifs that bind other partners. We hypothesized that if we identified the essential regions required for APC:Axin cooperative function and used these data to design a minimal β-catenin-destruction machine, we would gain new insights into the core mechanisms of destruction complex function. We identified five key domains/motifs in APC or Axin that are essential for their function in reconstituting Wnt regulation. Strikingly, however, certain APC and Axin mutants that are nonfunctional on their own can complement one another in reducing β-catenin, revealing that the APC:Axin complex is a highly robust machine. We used these insights to design a minimal β-catenin-destruction machine, revealing that a minimized chimeric protein covalently linking the five essential regions of APC and Axin reconstitutes destruction complex internal structure, size, and dynamics, restoring efficient β-catenin destruction in colorectal tumor cells. On the basis of our data, we propose a new model of the mechanistic function of the destruction complex as an integrated machine.

Indexed as

Adenomatous Polyposis Coli ProteinAnimalsAxin Proteinbeta CateninCell Line, TumorDrosophilaHumansPhosphorylationProtein DomainsRepressor ProteinsWnt ProteinsWnt Signaling PathwayAdenomatous Polyposis Coli ProteinAxin Proteinbeta CateninRepressor ProteinsWnt Proteins

Identifiers

PMID27852897
PMCPMC5221518
OpenAlexW2550630396

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.