Evidence map›Paper›PMID 25526088›Full record

ArticleCell death and differentiation2015

Spermidine induces autophagy by inhibiting the acetyltransferase EP300.

F Pietrocola, S Lachkar, D P Enot, M Niso-Santano, J M Bravo-San Pedro, V Sica, V Izzo, M C Maiuri, F Madeo, G Mariño and 1 more

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

Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
203citing papers in PubMed, 2 pooled it
8.6field-weighted citation impact, top 2% 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

203 citing papers in PubMed, 2 syntheses or guidelines pooled it, 320 citations in OpenAlex.

  1. Guideline
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  5. SAT1-Induced Spermidine Depletion Potentiates Food Allergy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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143 more citing papers are in PubMed but not listed here.

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

11 authors at 7 institutions in 2 countries.

F Pietrocola1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
S Lachkar1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
D P EnotMetabolomics and Molecular Cell Biology Platforms, Gustave Roussy, Villejuif 94805, France.
M Niso-Santano1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
J M Bravo-San Pedro1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
V Sica1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
V Izzo1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
M C Maiuri1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
F Madeo1] Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria [2] BioTechMed Graz, Graz 8010, Austria.
G Mariño1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
G Kroemer1] Equipe 11 labellisée par la Ligue Nationale contre le cancer, INSERM U1138, Centre de Recherche des Cordeliers, Paris 75006, France [2] Université Paris Descartes, Sorbonne Paris Cité, Paris, France [3] Metabolomics and Molecular Cell Biology Platforms, Gustave Roussy, Villejuif 94805, France [4] Université de Paris Sud, Villejuif 94805, France [5] Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris 75015, France.
Inserm · FRCentre de Recherche des Cordeliers · FRDélégation Paris 5 · FRInstitut Gustave Roussy · FRSorbonne Paris Cité · FRUniversité Paris Cité · FRUniversity of Graz · AT

Funding

Austrian Science Fund FWF I 1000Austrian Science Fund FWF P 23490Austrian Science Fund FWF P 24381
6 · The paper itself

Abstract

Several natural compounds found in health-related food items can inhibit acetyltransferases as they induce autophagy. Here we show that this applies to anacardic acid, curcumin, garcinol and spermidine, all of which reduce the acetylation level of cultured human cells as they induce signs of increased autophagic flux (such as the formation of green fluorescent protein-microtubule-associated protein 1A/1B-light chain 3 (GFP-LC3) puncta and the depletion of sequestosome-1, p62/SQSTM1) coupled to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1). We performed a screen to identify the acetyltransferases whose depletion would activate autophagy and simultaneously inhibit mTORC1. The knockdown of only two acetyltransferases (among 43 candidates) had such effects: EP300 (E1A-binding protein p300), which is a lysine acetyltranferase, and NAA20 (N(α)-acetyltransferase 20, also known as NAT5), which catalyzes the N-terminal acetylation of methionine residues. Subsequent studies validated the capacity of a pharmacological EP300 inhibitor, C646, to induce autophagy in both normal and enucleated cells (cytoplasts), underscoring the capacity of EP300 to repress autophagy by cytoplasmic (non-nuclear) effects. Notably, anacardic acid, curcumin, garcinol and spermidine all inhibited the acetyltransferase activity of recombinant EP300 protein in vitro. Altogether, these results support the idea that EP300 acts as an endogenous repressor of autophagy and that potent autophagy inducers including spermidine de facto act as EP300 inhibitors.

Indexed as

AutophagyCell Line, TumorE1A-Associated p300 ProteinHumansSpermidineE1A-Associated p300 ProteinEP300 protein, humanSpermidine

Identifiers

PMID25526088
PMCPMC4326581
OpenAlexW2059107485

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.