Evidence map›Paper›PMID 31936702›Full record

ArticleCells2020

Discovery and Preliminary Characterization of Translational Modulators that Impair the Binding of eIF6 to 60S Ribosomal Subunits.

Elisa Pesce, Annarita Miluzio, Lorenzo Turcano, Claudia Minici, Delia Cirino, Piera Calamita, Nicola Manfrini, Stefania Oliveto, Sara Ricciardi, Renata Grifantini and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

12 citing papers in PubMed, 19 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

13 authors at 4 institutions in 1 country.

Elisa PesceNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.ORCID 0000-0003-4214-1904
Annarita MiluzioNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.
Lorenzo TurcanoDepartment of Translational and Discovery Research, IRBM S.p.A., Via Pontina km 30, 600, 00071 Pomezia (Roma), Italy.
Claudia MiniciBiocrystallography Unit, Dept. of Immunology, Transplantation and Infectious Diseases, IRCCS Scientific Institute San Raffaele, Via Olgettina 58, 20132 Milan, Italy.ORCID 0000-0002-8350-484X
Delia CirinoNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.
Piera CalamitaNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.
Nicola ManfriniNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.
Stefania OlivetoNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.
Sara RicciardiNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.
Renata GrifantiniNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.
Massimo DeganoBiocrystallography Unit, Dept. of Immunology, Transplantation and Infectious Diseases, IRCCS Scientific Institute San Raffaele, Via Olgettina 58, 20132 Milan, Italy.
Alberto BrescianiDepartment of Translational and Discovery Research, IRBM S.p.A., Via Pontina km 30, 600, 00071 Pomezia (Roma), Italy.
Stefano BiffoNational Institute of Molecular Genetics, "Fondazione Romeo ed Enrica Invernizzi", INGM, Via Francesco Sforza 35, 20122 Milan, Italy.
University of Milan · ITIstituto Nazionale Genetica Molecolare · ITIRBM Science Park · ITVita-Salute San Raffaele University · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Eukaryotic initiation factor 6 (eIF6) is necessary for the nucleolar biogenesis of 60S ribosomes. However, most of eIF6 resides in the cytoplasm, where it acts as an initiation factor. eIF6 is necessary for maximal protein synthesis downstream of growth factor stimulation. eIF6 is an antiassociation factor that binds 60S subunits, in turn preventing premature 40S joining and thus the formation of inactive 80S subunits. It is widely thought that eIF6 antiassociation activity is critical for its function. Here, we exploited and improved our assay for eIF6 binding to ribosomes (iRIA) in order to screen for modulators of eIF6 binding to the 60S. Three compounds, eIFsixty-1 (clofazimine), eIFsixty-4, and eIFsixty-6 were identified and characterized. All three inhibit the binding of eIF6 to the 60S in the micromolar range. eIFsixty-4 robustly inhibits cell growth, whereas eIFsixty-1 and eIFsixty-6 might have dose- and cell-specific effects. Puromycin labeling shows that eIF6ixty-4 is a strong global translational inhibitor, whereas the other two are mild modulators. Polysome profiling and RT-qPCR show that all three inhibitors reduce the specific translation of well-known eIF6 targets. In contrast, none of them affect the nucleolar localization of eIF6. These data provide proof of principle that the generation of eIF6 translational modulators is feasible.

Indexed as

Protein BiosynthesisCell LineCell NucleolusCell SurvivalEnzyme-Linked Immunosorbent AssayHumansPeptide Chain Initiation, TranslationalPeptide Initiation FactorsPolyribosomesProtein BindingPuromycinReproducibility of ResultsRibosome Subunits, Large, EukaryoticRNA, MessengereIF-6Peptide Initiation FactorsPuromycinRNA, MessengereIF4EeIFsixty-iinitiationiRIApolysomesRACK1Shwachman–Diamond syndrome

Identifiers

PMID31936702
PMCPMC7017188
OpenAlexW3000171665

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.