Evidence map›Paper›PMID 27552662›Full record

ArticlePLoS biology2016

The Deubiquitinase USP47 Stabilizes MAPK by Counteracting the Function of the N-end Rule ligase POE/UBR4 in Drosophila.

Dariel Ashton-Beaucage, Caroline Lemieux, Christian M Udell, Malha Sahmi, Samuel Rochette, Marc Therrien

Open access · goldAbstract read
In one paragraph

Article in PLoS biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.7field-weighted citation impact, top 15% 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

30 citing papers in PubMed, 44 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

6 authors at 1 institution in 1 country.

Dariel Ashton-BeaucageInstitute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal, Montreal, Quebec, Canada.ORCID 0000-0001-6987-5487
Caroline LemieuxInstitute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal, Montreal, Quebec, Canada.
Christian M UdellInstitute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal, Montreal, Quebec, Canada.
Malha SahmiInstitute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal, Montreal, Quebec, Canada.
Samuel RochetteInstitute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal, Montreal, Quebec, Canada.
Marc TherrienInstitute for Research in Immunology and Cancer, Laboratory of Intracellular Signaling, Université de Montréal, Montreal, Quebec, Canada.
Institute for Research in Immunology and Cancer · CA

Funding

CIHR MOP-119443
6 · The paper itself

Abstract

RAS-induced MAPK signaling is a central driver of the cell proliferation apparatus. Disruption of this pathway is widely observed in cancer and other pathologies. Consequently, considerable effort has been devoted to understanding the mechanistic aspects of RAS-MAPK signal transmission and regulation. While much information has been garnered on the steps leading up to the activation and inactivation of core pathway components, comparatively little is known on the mechanisms controlling their expression and turnover. We recently identified several factors that dictate Drosophila MAPK levels. Here, we describe the function of one of these, the deubiquitinase (DUB) USP47. We found that USP47 acts post-translationally to counteract a proteasome-mediated event that reduces MAPK half-life and thereby dampens signaling output. Using an RNAi-based genetic interaction screening strategy, we identified UBC6, POE/UBR4, and UFD4, respectively, as E2 and E3 enzymes that oppose USP47 activity. Further characterization of POE-associated factors uncovered KCMF1 as another key component modulating MAPK levels. Together, these results identify a novel protein degradation module that governs MAPK levels. Given the role of UBR4 as an N-recognin ubiquitin ligase, our findings suggest that RAS-MAPK signaling in Drosophila is controlled by the N-end rule pathway and that USP47 counteracts its activity.

Indexed as

AnimalsAnimals, Genetically ModifiedCalmodulin-Binding ProteinsCell LineDrosophila melanogasterDrosophila ProteinsExtracellular Signal-Regulated MAP KinasesImmunoblottingIMP DehydrogenaseMAP Kinase Signaling SystemModels, BiologicalMutationProtein StabilityReverse Transcriptase Polymerase Chain ReactionRNA InterferenceUbiquitinationCalmodulin-Binding ProteinsDrosophila ProteinsExtracellular Signal-Regulated MAP KinasesIMP Dehydrogenasepoe protein, Drosophilaras protein, Drosophilarl protein, DrosophilaUbiquitin-Protein LigasesUbiquitin-Specific ProteasesUSP47 protein, Drosophila

Identifiers

PMID27552662
PMCPMC4994957
OpenAlexW2507955777

What OpenQuestion holds

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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.