Evidence map›Paper›PMID 29551266›Full record

ArticleCell2018

Multiplexed Proteome Dynamics Profiling Reveals Mechanisms Controlling Protein Homeostasis.

Mikhail M Savitski, Nico Zinn, Maria Faelth-Savitski, Daniel Poeckel, Stephan Gade, Isabelle Becher, Marcel Muelbaier, Anne J Wagner, Katrin Strohmer, Thilo Werner and 14 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
12.9field-weighted citation impact, top 1% 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

101 citing papers in PubMed, 223 citations in OpenAlex.

  1. mSphere · 2026
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  4. Hsp90: A means to an end.Cell stress & chaperones · 2026
    Review
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41 more citing papers are in PubMed but not listed here.

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

24 authors at 4 institutions in 3 countries.

Mikhail M SavitskiCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany; Genome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany. Electronic address: mikhail.savitski@embl.de.
Nico ZinnCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Maria Faelth-SavitskiCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Daniel PoeckelCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Stephan GadeCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Isabelle BecherGenome Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany.
Marcel MuelbaierCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Anne J WagnerCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Katrin StrohmerCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Thilo WernerCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Stephanie MelchertCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Massimo PetretichCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Anna RutkowskaCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Johanna VappianiCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Holger FrankenCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Michael SteidelCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Gavain M SweetmanCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Omer GilanCancer Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
Enid Y N LamCancer Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
Mark A DawsonCancer Research Division, Peter MacCallum Cancer Centre, East Melbourne, VIC 3002, Australia.
Rab K PrinjhaEpinova DPU, Immuno-Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK.
Paola GrandiCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Giovanna BergaminiCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: giovanna.2.bergamini@gsk.com.
Marcus BantscheffCellzome GmbH, GlaxoSmithKline, Meyerhofstrasse 1, 69117 Heidelberg, Germany. Electronic address: marcus.x.bantscheff@gsk.com.
GlaxoSmithKline (Germany) · DEPeter MacCallum Cancer Centre · AUEuropean Molecular Biology Laboratory · DEGlaxoSmithKline (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Protein degradation plays important roles in biological processes and is tightly regulated. Further, targeted proteolysis is an emerging research tool and therapeutic strategy. However, proteome-wide technologies to investigate the causes and consequences of protein degradation in biological systems are lacking. We developed "multiplexed proteome dynamics profiling" (mPDP), a mass-spectrometry-based approach combining dynamic-SILAC labeling with isobaric mass tagging for multiplexed analysis of protein degradation and synthesis. In three proof-of-concept studies, we uncover different responses induced by the bromodomain inhibitor JQ1 versus a JQ1 proteolysis targeting chimera; we elucidate distinct modes of action of estrogen receptor modulators; and we comprehensively classify HSP90 clients based on their requirement for HSP90 constitutively or during synthesis, demonstrating that constitutive HSP90 clients have lower thermal stability than non-clients, have higher affinity for the chaperone, vary between cell types, and change upon external stimuli. These findings highlight the potential of mPDP to identify dynamically controlled degradation mechanisms in cellular systems.

Indexed as

AzepinesBromodomain Containing ProteinsCell LineChromatography, High Pressure LiquidCluster AnalysisEstradiolHSP90 Heat-Shock ProteinsHumansIsotope LabelingJurkat CellsMCF-7 CellsNeoplasm ProteinsProteinsProteolysisProteomeProteomicsAzepinesbromodomain and extra-terminal domain protein, humanBromodomain Containing ProteinsEstradiolGREB1 protein, humanHSP90 Heat-Shock Proteins(+)-JQ1 compoundNeoplasm ProteinsProteinsProteomeReceptors, EstrogenTriazolesdegradationestrogen receptorHSP90JQ1mass spectrometrymechanism-of-actionPROTACprotein turnoverproteostasis

Identifiers

PMID29551266
PMCPMC5871718
OpenAlexW2791501381

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.