Evidence map›Paper›PMID 23056511›Full record

ArticlePloS one2012

The JNK- and AKT/GSK3β- signaling pathways converge to regulate Puma induction and neuronal apoptosis induced by trophic factor deprivation.

Kristin K Ambacher, Kristen B Pitzul, Meera Karajgikar, Alison Hamilton, Stephen S Ferguson, Sean P Cregan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

57 citing papers in PubMed, 85 citations in OpenAlex.

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  12. Autophagy and apoptosis cascade: which is more prominent in neuronal death?Cellular and molecular life sciences : CMLS · 2021
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  14. A High-Throughput Chemical Screen in DJ-1β Mutant Flies Identifies Zaprinast as a Potential Parkinson's Disease Treatment.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021
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  19. Cannabidiol and the Canonical WNT/β-Catenin Pathway in Glaucoma.International journal of molecular sciences · 2021
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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

6 authors at 1 institution in 1 country.

Kristin K AmbacherRobarts Research Institute and Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Kristen B Pitzul
Meera Karajgikar
Alison Hamilton
Stephen S Ferguson
Sean P Cregan
Western University · CA

Funding

Canadian Institutes of Health Research MOP-68995
6 · The paper itself

Abstract

The AKT, GSK3 and JNK family kinases have been implicated in neuronal apoptosis associated with neuronal development and several neurodegenerative conditions. However, the mechanisms by which these kinase pathways regulate apoptosis remain unclear. In this study we have investigated the role of these kinases in neuronal cell death using an established model of trophic factor deprivation induced apoptosis in cerebellar granule neurons. BCL-2 family proteins are known to be central regulators of apoptosis and we have determined that the pro-apoptotic family member Puma is transcriptionally up-regulated in trophic factor deprived neurons and that Puma induction is required for apoptosis in vitro and in vivo. Importantly, we demonstrate that Puma induction is dependent on both JNK activation and AKT inactivation. AKT is known to regulate a number of downstream pathways, however we have determined that PI3K-AKT inactivation induces Puma expression through a GSK3β-dependent mechanism. Finally we demonstrate that the JNK and AKT/GSK3β pathways converge to regulate FoxO3a-mediated transcriptional activation of Puma. In summary we have identified a novel and critical link between the AKT, GSK3β and JNK kinases and the regulation of Puma induction and suggest that this may be pivotal to the regulation of neuronal apoptosis in neurodegenerative conditions.

Indexed as

ApoptosisSignal TransductionAnimalsApoptosis Regulatory ProteinsEnzyme ActivationForkhead Box Protein O3Forkhead Transcription FactorsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaIntercellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesMiceNeuronsPotassiumProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktApoptosis Regulatory ProteinsForkhead Box Protein O3Forkhead Transcription FactorsFoxO3 protein, mouseGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGsk3b protein, mouseIntercellular Signaling Peptides and ProteinsJNK Mitogen-Activated Protein KinasesPotassiumProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPUMA protein, mouseTumor Suppressor Proteins

Identifiers

PMID23056511
PMCPMC3463558
OpenAlexW2091070768

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.