Evidence map›Paper›PMID 27996937›Full record

ArticleeLife2016

Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling.

Andres M Lebensohn, Ramin Dubey, Leif R Neitzel, Ofelia Tacchelly-Benites, Eungi Yang, Caleb D Marceau, Eric M Davis, Bhaven B Patel, Zahra Bahrami-Nejad, Kyle J Travaglini and 4 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

44 citing papers in PubMed, 64 citations in OpenAlex.

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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

14 authors at 4 institutions in 1 country.

Andres M LebensohnDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0002-4224-8819
Ramin DubeyDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.
Leif R NeitzelDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, United States.
Ofelia Tacchelly-BenitesDepartment of Molecular and Systems Biology and the Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, United States.
Eungi YangDepartment of Molecular and Systems Biology and the Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, United States.
Caleb D MarceauDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States.
Eric M DavisDepartment of Molecular Cellular, and Developmental Biology, University of Colorado, Boulder, Boulder, United States.
Bhaven B PatelDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.
Zahra Bahrami-NejadDepartment of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States.
Kyle J TravagliniDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.
Yashi AhmedDepartment of Molecular and Systems Biology and the Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, United States.
Ethan LeeDepartment of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, United States.
Jan E CaretteDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, United States.
Rajat RohatgiDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United States.ORCID 0000-0001-7609-8858
Stanford University · USDartmouth College · USVanderbilt University Medical Center · USUniversity of Colorado Boulder · US

Funding

Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
MOLECULAR BASIS OF HOST-PARASITE INTERACTIONT32AI007328 · NIAID · STANFORD UNIVERSITY · PI JUSTIN L SONNENBURG · 1987 to 2026
$11.9M
Supplement application for an Olympus automated microscopeR35GM118082 · NIGMS · STANFORD UNIVERSITY · PI RAJAT ROHATGI · 2016 to 2026
$7.6M
Training Program in Stem Cell and Regenerative Developmental BiologyT32HD007502 · NICHD · VANDERBILT UNIVERSITY · PI WRIGHT, CHRISTOPHER V · 1997 to 2022
$5.4M
APC Tumor Suppressor in Cell Differentiation and DeathR01CA105038 · NCI · DARTMOUTH COLLEGE · PI AHMED, YASMATH · 2005 to 2016
$2.6M
Regulation of beta-catenin degradation during Wnt signal transductionR01GM081635 · NIGMS · VANDERBILT UNIVERSITY · PI LEE, ETHAN · 2007 to 2016
$2.4M
Reconstructing Primary CiliaDP2GM105448 · NIGMS · STANFORD UNIVERSITY · PI ROHATGI, RAJAT · 2012 to 2012
$2.4M
Genetic approaches to discover host factors critical to dengue virus infectionDP2AI104557 · NIAID · STANFORD UNIVERSITY · PI CARETTE, JAN E · 2012 to 2012
$2.3M
Role of ubiquitination in the Wnt pathwayR01GM103926 · NIGMS · VANDERBILT UNIVERSITY · PI LEE, ETHAN · 2013 to 2016
$1.2M
APC Tumor Suppressor in Cell Differentiation and DeathR01GM122222 · NIGMS · DARTMOUTH COLLEGE · PI AHMED, YASMATH · 2017 to 2019
$977k
NCI NIH HHS R01 CA105038NIAID NIH HHS DP2 AI104557NIAID NIH HHS T32 AI007328NIAID NIH HHS U19 AI109662NICHD NIH HHS T32 HD007502NIGMS NIH HHS DP2 GM105448NIGMS NIH HHS R01 GM081635NIGMS NIH HHS R01 GM103926NIGMS NIH HHS R35 GM118082
6 · The paper itself

Abstract

The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway. These include a requirement for the transcription factor AP-4, a role for the DAX domain of AXIN2 in controlling β-catenin transcriptional activity, a contribution of glycophosphatidylinositol anchor biosynthesis and glypicans to R-spondin-potentiated WNT signaling, and two different mechanisms that regulate signaling when distinct components of the β-catenin destruction complex are lost. The conceptual and methodological framework we describe should enable the comprehensive understanding of other signaling systems.

Indexed as

Gene Expression RegulationGene Regulatory NetworksWnt Signaling PathwayCasein Kinase ICytoskeletal ProteinsGenes, ReporterGenetic TestingHaploidyHumansWnt ProteinsAPC2 protein, humanCasein Kinase ICytoskeletal ProteinsWnt ProteinsAPCAXINcomputational biologyCSNK1A1developmental biologyforward geneticsgenetic screenglypicanGPC4GPIHAP1haploid cellshaploid screenhumanHUWE1RSPOSERBP1stem cellssuppressor screensystems biologyTFAP4WNT signaling

Identifiers

PMID27996937
PMCPMC5257257
OpenAlexW2564219375

What OpenQuestion holds

Textmetadata
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.