Evidence map›Paper›PMID 20181828›Full record

ArticleMolecular biology of the cell2010

Deficiency of the transcriptional regulator p8 results in increased autophagy and apoptosis, and causes impaired heart function.

Derek K Kong, Serban P Georgescu, Carla Cano, Mark J Aronovitz, Juan Lucio Iovanna, Richard D Patten, John M Kyriakis, Sandro Goruppi

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 2 pooled it
3.8field-weighted citation impact, top 7% 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

33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.

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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

8 authors at 4 institutions in 2 countries.

Derek K KongMolecular Cardiology Research Institute, Tufts Medical Center and Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA.
Serban P Georgescu
Carla Cano
Mark J Aronovitz
Juan Lucio Iovanna
Richard D Patten
John M Kyriakis
Sandro Goruppi
Tufts University · USInserm · FRInstitut de Neurobiologie de la Méditerranée · FRTufts Medical Center · US

Funding

MLK3 function in neurofibromatosis tumor cellsR01CA112399 · NCI · TUFTS MEDICAL CENTER · PI KYRIAKIS, JOHN M · 2005 to 2009
$1.2M
NCI NIH HHS R01 CA112399NCI NIH HHS R01-CA112399
6 · The paper itself

Abstract

Autophagy is a cytoprotective pathway used to degrade and recycle cytoplasmic content. Dysfunctional autophagy has been linked to both cancer and cardiomyopathies. Here, we show a role for the transcriptional regulator p8 in autophagy. p8 RNA interference (RNAi) increases basal autophagy markers in primary cardiomyocytes, in H9C2 and U2OS cells, and decreases cellular viability after autophagy induction. This autophagy is associated with caspase activation and is blocked by atg5 silencing and by pharmacological inhibitors. FoxO3 transcription factor was reported to activate autophagy by enhancing the expression of autophagy-related genes. P8 expression represses FoxO3 transcriptional activity, and p8 knockdown affects FoxO3 nuclear localization. Thus, p8 RNAi increases FoxO3 association with bnip3 promoter, a known proautophagic FoxO3 target, resulting in higher bnip3 RNA and protein levels. Accordingly, bnip3 knockdown restores cell viability and blocks apoptosis of p8-deficient cells. In vivo, p8 -/- mice have higher autophagy and express higher cardiac bnip3 levels. These mice develop left ventricular wall thinning and chamber dilation, with consequent impaired cardiac function. Our studies provide evidence of a p8-dependent mechanism regulating autophagy by acting as FoxO3 corepressor, which may be relevant for diseases associated with dysregulated autophagy, as cardiovascular pathologies and cancer.

Indexed as

ApoptosisAutophagyHeart Function TestsAnimalsBasic Helix-Loop-Helix ProteinsCarrier ProteinsCell LineDNA-Binding ProteinsEnergy MetabolismForkhead Box Protein O3Forkhead Transcription FactorsGene DeletionGene SilencingHeartHumansMembrane ProteinsBasic Helix-Loop-Helix ProteinsBNIP3 protein, humanCarrier ProteinsDNA-Binding ProteinsForkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanMembrane ProteinsNeoplasm ProteinsNUPR1 protein, humanNupr1 protein, mouseNupr1 protein, ratProto-Oncogene ProteinsRepressor ProteinsRNA, MessengerRnf19 protein, mouseUbiquitin-Protein Ligases

Identifiers

PMID20181828
PMCPMC2854092
OpenAlexW2119366144

What OpenQuestion holds

Textmetadata
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.