期刊
CELL REPORTS
卷 22, 期 9, 页码 2395-2407出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.02.024
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资金
- Ligue contre le Cancer Comitede Charente-Maritime (equipe labelisee)
- Agence National de la Recherche (ANR) - Projets blancs
- ANR
- Association pour la recherche sur le cancer (ARC)
- Canceropole Ile-de-France
- Chancelerie des universites de Paris (Legs Poix), Fondation pour la Recherche Medicale (FRM)
- European Commission (ArtForce)
- European Research Council (ERC) [ERC-2012-AdG-320339-Immunodeath]
- Fondation Carrefour
- Institut National du Cancer (INCa)
- INSERM (HTE)
- Institut Universitaire de France
- LeDucq Foundation
- LabEx Immuno-Oncology
- RHU Torino Lumiere
- Searave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Paris Alliance of Cancer Research Institutes (PACRI)
- FWF [P 29262, P 27893, P 29203, P24381-B20, 80.109/0001 -WF/V/3b/2015]
- Ramon y Cajal Program [RYC-2013-12751]
- Spain's Ministerio de Economia y Competitividad [BFU2015-68539]
- BBVA Foundation [SV-15-FBBVA-2]
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- Austrian Science Fund (FWF) [P29262, P29203] Funding Source: Austrian Science Fund (FWF)
The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways and disabled autophagy. The reactivation of autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed with the capacity to reduce the overall levels of protein acetylation and to induce autophagy have been categorized as caloric restriction mimetics (CRMs). Here, we show that aspirin or its active metabolite salicylate induce autophagy by virtue of their capacity to inhibit the acetyltransferase activity of EP300. While salicylate readily stimulates autophagic flux in control cells, it fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants. Accordingly, the proautophagic activity of aspirin and salicylate on the nematode Caenorhabditis elegans is lost when the expression of the EP300 ortholog cpb-1 is reduced. Altogether, these findings identify aspirin as an evolutionary conserved CRM.
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