Evidence map›Paper›PMID 32589666›Full record

ArticlePLoS computational biology2020

A systematic approach to decipher crosstalk in the p53 signaling pathway using single cell dynamics.

Fabian Konrath, Anna Mittermeier, Elena Cristiano, Jana Wolf, Alexander Loewer

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.1field-weighted citation impact, top 20% 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

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
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  7. Perspectives in Plant Abiotic Stress Signaling.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
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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

5 authors at 2 institutions in 1 country.

Fabian KonrathMathematical Modelling of Cellular Processes, Max Delbrueck Center for Molecular Medicine, Berlin, Germany.ORCID 0000-0002-6843-6252
Anna MittermeierSystems Biology of the Stress Response, Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany.ORCID 0000-0001-8439-4307
Elena CristianoSignaling Dynamics in Single Cells, Berlin Institute for Medical Systems Biology, Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
Jana WolfMathematical Modelling of Cellular Processes, Max Delbrueck Center for Molecular Medicine, Berlin, Germany.ORCID 0000-0003-3254-5868
Alexander LoewerSystems Biology of the Stress Response, Department of Biology, Technische Universität Darmstadt, Darmstadt, Germany.ORCID 0000-0002-8819-3040
Max Delbrück Center · DETechnische Universität Darmstadt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The transcription factors NF-κB and p53 are key regulators in the genotoxic stress response and are critical for tumor development. Although there is ample evidence for interactions between both networks, a comprehensive understanding of the crosstalk is lacking. Here, we developed a systematic approach to identify potential interactions between the pathways. We perturbed NF-κB signaling by inhibiting IKK2, a critical regulator of NF-κB activity, and monitored the altered response of p53 to genotoxic stress using single cell time lapse microscopy. Fitting subpopulation-specific computational p53 models to this time-resolved single cell data allowed to reproduce in a quantitative manner signaling dynamics and cellular heterogeneity for the unperturbed and perturbed conditions. The approach enabled us to untangle the integrated effects of IKK/ NF-κB perturbation on p53 dynamics and thereby derive potential interactions between both networks. Intriguingly, we find that a simultaneous perturbation of multiple processes is necessary to explain the observed changes in the p53 response. Specifically, we show interference with the activation and degradation of p53 as well as the degradation of Mdm2. Our results highlight the importance of the crosstalk and its potential implications in p53-dependent cellular functions.

Indexed as

Single-Cell AnalysisMicroscopyNF-kappa BReproducibility of ResultsSignal TransductionTumor Suppressor Protein p53NF-kappa BTumor Suppressor Protein p53

Identifiers

PMID32589666
PMCPMC7319280
OpenAlexW3037518185

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.