Evidence map›Paper›PMID 32006464›Full record

ArticleMolecular cell2020

Localized Inhibition of Protein Phosphatase 1 by NUAK1 Promotes Spliceosome Activity and Reveals a MYC-Sensitive Feedback Control of Transcription.

Giacomo Cossa, Isabelle Roeschert, Florian Prinz, Apoorva Baluapuri, Raphael Silveira Vidal, Christina Schülein-Völk, Yun-Chien Chang, Carsten Patrick Ade, Guido Mastrobuoni, Cyrille Girard and 8 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.1field-weighted citation impact, top 7% 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, 62 citations in OpenAlex.

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  11. Using evolutionary constraint to define novel candidate driver genes in medulloblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 1 country.

Giacomo CossaDepartment of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Isabelle RoeschertDepartment of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Florian PrinzLab GBM Research 5, Research & Development, Pharmaceuticals, Bayer AG, Building S155, 13342 Berlin, Germany.
Apoorva BaluapuriCancer Systems Biology Group, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Raphael Silveira VidalDepartment of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Christina Schülein-VölkDepartment of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Yun-Chien ChangTechnical University of Munich, Emil-Erlenmeyer Forum 5, 85354 Freising, Germany.
Carsten Patrick AdeDepartment of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Guido MastrobuoniBerlin Institute for Medical Systems Biology at The Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Cyrille GirardDepartment of Cellular Biochemistry, Max-Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Lars WortmannLab GBM Research 5, Research & Development, Pharmaceuticals, Bayer AG, Building S155, 13342 Berlin, Germany.
Susanne WalzComprehensive Cancer Center Mainfranken, Core Unit Bioinformatics, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Reinhard LührmannDepartment of Cellular Biochemistry, Max-Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Stefan KempaBerlin Institute for Medical Systems Biology at The Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Bernhard KusterTechnical University of Munich, Emil-Erlenmeyer Forum 5, 85354 Freising, Germany.
Elmar WolfCancer Systems Biology Group, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Dominik MumbergLab GBM Research 5, Research & Development, Pharmaceuticals, Bayer AG, Building S155, 13342 Berlin, Germany.
Martin EilersDepartment of Biochemistry and Molecular Biology, Biocenter, University of Würzburg, Am Hubland, 97074 Würzburg, Germany. Electronic address: martin.eilers@biozentrum.uni-wuerzburg.de.
University of Würzburg · DEBayer (Germany) · DEMax Delbrück Center · DEMax Planck Institute for Biophysical Chemistry · DETechnical University of Munich · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but the molecular mechanisms underlying this dependence have not been fully clarified. Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1. Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. Activation of MYC does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. Consequently, NUAK1 inhibition in MYC-transformed cells induces global accumulation of RNAPII both at the pause site and at the first exon-intron boundary but does not increase mRNA synthesis. We suggest that NUAK1 inhibition in the presence of deregulated MYC traps non-productive RNAPII because of the absence of correctly assembled spliceosomes.

Indexed as

Transcription, GeneticAnimalsCell NucleusChromatinGene Expression RegulationHeLa CellsHumansMiceNIH 3T3 CellsPhosphorylationProtein KinasesProtein Phosphatase 1Proto-Oncogene Proteins c-mycRepressor ProteinsRNA Polymerase IIRNA SplicingChromatinMYC protein, humanNUAK1 protein, humanProtein KinasesProtein Phosphatase 1Proto-Oncogene Proteins c-mycRepressor ProteinsRNA Polymerase IIARK5MYCNUAK1PNUTSPP1Protein Phosphatase 1Spliceosome

Identifiers

PMID32006464
PMCPMC7086158
OpenAlexW3003719244

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.