Evidence map›Paper›PMID 29686375›Full record

ArticleCell death & disease2018

Requirement of GSK-3 for PUMA induction upon loss of pro-survival PI3K signaling.

Florian Schubert, Juliane Rapp, Prisca Brauns-Schubert, Lisa Schlicher, Kerstin Stock, Manuela Wissler, Martina Weiß, Céline Charvet, Christoph Borner, Ulrich Maurer

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.5field-weighted citation impact, top 37% 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

7 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Combined BCL-2 and PI3K/AKT Pathway Inhibition inInternational journal of molecular sciences · 2023
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. 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

10 authors at 2 institutions in 2 countries.

Florian SchubertInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Juliane RappInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Prisca Brauns-SchubertInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Lisa SchlicherInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Kerstin StockInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Manuela WisslerInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Martina WeißInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Céline CharvetFunctional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR 7104, Université de Strasbourg, 1 rue Laurent Fries, Illkirch, 67404, France.
Christoph BornerInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany.
Ulrich MaurerInstitute of Molecular Medicine and Cell Research, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany. ulrich.maurer@mol-med.uni-freiburg.de.ORCID 0000-0002-2504-1517
University of Freiburg · DECentre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Growth factor withdrawal induces rapid apoptosis via mitochondrial outer membrane permeabilization. We had previously observed that cell death of IL-3-dependent Ba/F3 cells, induced by removal of the growth factor, required the activity of the kinase GSK-3. Employing CRISPR/Cas9-mediated gene knockout, we aimed to identify pro-apoptotic GSK-3 regulated factors in this process. Knockout of either Puma or Bim demonstrated that the induction of Puma, but not Bim, was crucial for apoptosis induced by IL-3 deprivation. Thus, we aimed at identifying the GSK-3-dependent PUMA regulator. Loss of FOXO3A reduced the induction of Puma, while additional loss of p53 completely repressed induction upon growth factor withdrawal. A constitutively active mutant of FOXO3A, which cannot be controlled by AKT directly, still required active GSK-3 for the full transcriptional induction of Puma and cell death upon IL-3 withdrawal. Thus, the suppression of GSK-3 is the key function of PI3K signaling in order to prevent the induction of Puma by FOXO3A and p53 and thereby apoptosis upon growth factor withdrawal.

Indexed as

ApoptosisSignal TransductionApoptosis Regulatory ProteinsGlycogen Synthase Kinase 3HCT116 CellsHEK293 CellsHumansPhosphatidylinositol 3-KinasesProto-Oncogene ProteinsApoptosis Regulatory ProteinsBBC3 protein, humanGlycogen Synthase Kinase 3Phosphatidylinositol 3-KinasesProto-Oncogene Proteins

Identifiers

PMID29686375
PMCPMC5913275
OpenAlexW2801099536

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.