Evidence map›Paper›PMID 21677192›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2011

A haploid genetic screen identifies the major facilitator domain containing 2A (MFSD2A) transporter as a key mediator in the response to tunicamycin.

Jan H Reiling, Clary B Clish, Jan E Carette, Malini Varadarajan, Thijn R Brummelkamp, David M Sabatini

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

66 citing papers in PubMed, 107 citations in OpenAlex.

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  10. Defective Thyroglobulin: Cell Biology of Disease.International journal of molecular sciences · 2022
    Review
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  20. Galectin-1 interacts with the human endogenous retroviral envelope protein syncytin-2 and potentiates trophoblast fusion in humans.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019
    Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Jan H ReilingWhitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Clary B Clish
Jan E Carette
Malini Varadarajan
Thijn R Brummelkamp
David M Sabatini
Whitehead Institute for Biomedical Research · USBroad Institute · USHoward Hughes Medical Institute · USStanford University · US

Funding

Regulation of the mTOR Pathway By NutrientsR01CA103866 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2004 to 2021
$7.0M
Cell Growth Signaling in Cancer DevelopmentR01CA129105 · NCI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI WEISSMAN, JONATHAN S. · 2008 to 2021
$5.9M
A new system for mammalian cell genetics using a haploid genomic contextR21HG004938 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI BRUMMELKAMP, THIJN · 2009 to 2010
$536k
Howard Hughes Medical InstituteNCI NIH HHS CA103866NCI NIH HHS CA129105NCI NIH HHS R01 CA103866NCI NIH HHS R01 CA129105NHGRI NIH HHS R21 HG004938NHGRI NIH HHS R21 HG004938-01
6 · The paper itself

Abstract

Tunicamycin (TM) inhibits eukaryotic asparagine-linked glycosylation, protein palmitoylation, ganglioside production, proteoglycan synthesis, 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity, and cell wall biosynthesis in bacteria. Treatment of cells with TM elicits endoplasmic reticulum stress and activates the unfolded protein response. Although widely used in laboratory settings for many years, it is unknown how TM enters cells. Here, we identify in an unbiased genetic screen a transporter of the major facilitator superfamily, major facilitator domain containing 2A (MFSD2A), as a critical mediator of TM toxicity. Cells without MFSD2A are TM-resistant, whereas MFSD2A-overexpressing cells are hypersensitive. Hypersensitivity is associated with increased cellular TM uptake concomitant with an enhanced endoplasmic reticulum stress response. Furthermore, MFSD2A mutant analysis reveals an important function of the C terminus for correct intracellular localization and protein stability, and it identifies transmembrane helical amino acid residues essential for mediating TM sensitivity. Overall, our data uncover a critical role for MFSD2A by acting as a putative TM transporter at the plasma membrane.

Indexed as

Blotting, WesternCell LineCell SurvivalEndoplasmic ReticulumGlycosylationHumansImmunoprecipitationMembrane Transport ProteinsMicroscopy, ConfocalProtein FoldingSignal TransductionSymportersTumor Suppressor ProteinsTunicamycinMembrane Transport ProteinsMFSD2A protein, humanSymportersTumor Suppressor ProteinsTunicamycin

Identifiers

PMID21677192
PMCPMC3141996
OpenAlexW2066741833

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.