Evidence map›Paper›PMID 28468958›Full record

ArticleMolecular systems biology2017

An immediate-late gene expression module decodes ERK signal duration.

Florian Uhlitz, Anja Sieber, Emanuel Wyler, Raphaela Fritsche-Guenther, Johannes Meisig, Markus Landthaler, Bertram Klinger, Nils Blüthgen

Erratum issuedAbstract read
In one paragraph

Article in Molecular systems biology, 2017. 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 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
–field-weighted citation impact
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

40 citing papers in PubMed.

  1. Article
  2. Enzymatic DNA Reaction Networks for Orchestrating Stimuli-Dependent Temporal Molecular Pulse.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  11. bioRxiv : the preprint server for biology · 2024
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  16. Article
  17. Zoological research · 2023
    Article
  18. Article
  19. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Florian UhlitzIRI Life Sciences & Institute for Theoretical Biology, Humboldt Universität Berlin, Berlin, Germany.ORCID 0000-0001-9176-4660
Anja SieberIRI Life Sciences & Institute for Theoretical Biology, Humboldt Universität Berlin, Berlin, Germany.
Emanuel WylerBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Raphaela Fritsche-GuentherBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Johannes MeisigIRI Life Sciences & Institute for Theoretical Biology, Humboldt Universität Berlin, Berlin, Germany.
Markus LandthalerBerlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Bertram KlingerIRI Life Sciences & Institute for Theoretical Biology, Humboldt Universität Berlin, Berlin, Germany.
Nils BlüthgenIRI Life Sciences & Institute for Theoretical Biology, Humboldt Universität Berlin, Berlin, Germany nils.bluethgen@charite.de.ORCID 0000-0002-0171-7447

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The RAF-MEK-ERK signalling pathway controls fundamental, often opposing cellular processes such as proliferation and apoptosis. Signal duration has been identified to play a decisive role in these cell fate decisions. However, it remains unclear how the different early and late responding gene expression modules can discriminate short and long signals. We obtained both protein phosphorylation and gene expression time course data from HEK293 cells carrying an inducible construct of the proto-oncogene RAF By mathematical modelling, we identified a new gene expression module of immediate-late genes (ILGs) distinct in gene expression dynamics and function. We find that mRNA longevity enables these ILGs to respond late and thus translate ERK signal duration into response amplitude. Despite their late response, their GC-rich promoter structure suggested and metabolic labelling with 4SU confirmed that transcription of ILGs is induced immediately. A comparative analysis shows that the principle of duration decoding is conserved in PC12 cells and MCF7 cells, two paradigm cell systems for ERK signal duration. Altogether, our findings suggest that ILGs function as a gene expression module to decode ERK signal duration.

Indexed as

Gene Expression RegulationAnimalsComputer SimulationGC Rich SequenceHalf-LifeHEK293 CellsHumansMAP Kinase Signaling SystemMCF-7 CellsModels, TheoreticalMultigene FamilyPC12 CellsPromoter Regions, GeneticProto-Oncogene Masraf KinasesRatsMAS1 protein, humanProto-Oncogene Masraf KinasesRNA, MessengerERK signallingimmediate–late genesmRNA half‐lifesignal decodingsignal duration

Identifiers

PMID28468958
PMCPMC5448165

What OpenQuestion holds

Textmetadata
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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.