Evidence map›Paper›PMID 31056462›Full record

ArticleCell chemical biology2019

Chemoproteomic Profiling Uncovers CDK4-Mediated Phosphorylation of the Translational Suppressor 4E-BP1.

Dylan C Mitchell, Arya Menon, Amanda L Garner

Open access · bronzeAbstract read
In one paragraph

Article in Cell chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 32% 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

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
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  6. The RNA-binding protein SART3 promotes miR-34a biogenesis and GThe Journal of biological chemistry · 2019
    Article
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

3 authors at 1 institution in 1 country.

Dylan C MitchellProgram in Chemical Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Arya MenonDepartment of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
Amanda L GarnerProgram in Chemical Biology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: algarner@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Research Training in BiogerontologyT32AG000114 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCOTT PLETCHER · 1985 to 2026
$12.4M
Proteogenomics of Cancer Training ProgramT32CA140044 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAO, ARVIND, SARTOR, MAUREEN AGNES · 2010 to 2024
$3.9M
4E-BP Mimetics as Chemical Probes for Studying Translational Control in CancerR01CA202018 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GARNER, AMANDA · 2016 to 2020
$1.8M
NCI NIH HHS R01 CA202018NCI NIH HHS T32 CA140044NIA NIH HHS T32 AG000114
6 · The paper itself

Abstract

Recent estimates of the human proteome suggest there are ∼20,000 protein-coding genes, the protein products of which contain >145,000 phosphosites. Unfortunately, in-depth examination of the human phosphoproteome has outpaced the ability to annotate the kinases that mediate these post-translational modifications. To obtain actionable information about phosphorylation-driven signaling cascades, it is essential to identify the kinases responsible for phosphorylating sites that differ across disease states. To fill in these gaps we have developed an unbiased, chemoproteomic approach for identifying high-confidence kinase-substrate interactions with phosphosite specificity. Using this assay, we uncovered the role of cyclin-dependent kinase 4 (CDK4), a clinically validated kinase important for cell-cycle progression, in regulating cap-dependent translation via phosphorylation of the tumor suppressor 4E-BP1. The discovery of this signaling axis sheds light on the mechanisms by which CDK4/6 inhibitors control cell proliferation and constitutes a successful example of kinase discovery using an activity-based, kinase-directed probe.

Indexed as

Adaptor Proteins, Signal TransducingAdolescentCell Cycle ProteinsCell Line, TumorCell ProliferationCyclin-Dependent Kinase 4FemaleHEK293 CellsHeLa CellsHigh-Throughput Screening AssaysHumansMCF-7 CellsMiddle AgedPhosphorylationProtein BindingProtein Processing, Post-TranslationalAdaptor Proteins, Signal TransducingCDK4 protein, humanCell Cycle ProteinsCyclin-Dependent Kinase 4EIF4EBP1 protein, humanTOR Serine-Threonine Kinases4E-BP1CDK4chemoproteomicskinasesmTORC1phosphorylationtranslation

Identifiers

PMID31056462
PMCPMC6642002
OpenAlexW2942927073

What OpenQuestion holds

Textmetadata
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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.