title: BAT3 modulates p300-dependent acetylation of p53 and autophagy-related protein 7 (ATG7) during autophagy.
abstract: Autophagy is regulated by posttranslational modifications, including acetylation. Here we show that HLA-B-associated transcript 3 (BAT3) is essential for basal and starvation-induced autophagy in embryonic day 18.5 BAT3(-/-) mouse embryos and in mouse embryonic fibroblasts (MEFs) through the modulation of p300-dependent acetylation of p53 and ATG7. Specifically, BAT3 increases p53 acetylation and proautophagic p53 target gene expression, while limiting p300-dependent acetylation of ATG7, a mechanism known to inhibit autophagy. In the absence of BAT3 or when BAT3 is located exclusively in the cytosol, autophagy is abrogated, ATG7 is hyperacetylated, p53 acetylation is abolished, and p300 accumulates in the cytosol, indicating that BAT3 regulates the nuclear localization of p300. In addition, the interaction between BAT3 and p300 is stronger in the cytosol than in the nucleus and, during starvation, the level of p300 decreases in the cytosol but increases in the nucleus only in the presence of BAT3. We conclude that BAT3 tightly controls autophagy by modulating p300 intracellular localization, affecting the accessibility of p300 to its substrates, p53 and ATG7.
authors.affiliation: Institut de Recherche en Cancérologie de Montpellier, F-34298 Montpellier, France.
authors.forename: Salwa
authors.initials: S
authors.lastname: Sebti
authors.forename: Christine
authors.initials: C
authors.lastname: Prébois
authors.forename: Esther
authors.initials: E
authors.lastname: Pérez-Gracia
authors.forename: Chantal
authors.initials: C
authors.lastname: Bauvy
authors.forename: Fabienne
authors.initials: F
authors.lastname: Desmots
authors.forename: Nelly
authors.initials: N
authors.lastname: Pirot
authors.forename: Céline
authors.initials: C
authors.lastname: Gongora
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Bach
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Hubberstey
authors.forename: Valérie
authors.initials: V
authors.lastname: Palissot
authors.forename: Guy
authors.initials: G
authors.lastname: Berchem
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.forename: Laetitia K
authors.initials: LK
authors.lastname: Linares
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Liaudet-Coopman
authors.forename: Sophie
authors.initials: S
authors.lastname: Pattingre
mesh_terms: D000107:Acetylation; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism / Q000502:physiology*; D047468:Immunoprecipitation; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C502661:Atg7 protein, mouse; C484266:Bag6 protein, mouse; D017931:DNA Primers; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse; D000071193:Autophagy-Related Protein 7
keywords: degradation; nucleo-cytoplasmic shuttling; signalisation