BAG6/BAT3 modulates autophagy by affecting EP300/p300 intracellular localization.
We recently reported that BAG6/BAT3 (BCL2-associated athanogene 6) is essential for basal and starvation-induced autophagy in E18.5 bag6(-/-) mouse embryos and in mouse embryonic fibroblasts (MEFs) through the modulation of the EP300/p300-dependent acetylation of TRP53 and autophagy-related (ATG) proteins. We observed that BAG6 increases TRP53 acetylation during starvation and pro-autophagic TRP53-target gene expression. BAG6 also decreases the EP300 dependent-acetylation of ATG5, ATG7, and LC3-I, posttranslational modifications that inhibit autophagy. In addition, in the absence of BAG6 or when using a mutant of BAG6 exclusively located in the cytoplasm, autophagy is inhibited, ATG7 is hyperacetylated, TRP53 acetylation is abrogated, and EP300 accumulates in the cytoplasm indicating that BAG6 is involved in the regulation of the nuclear localization of EP300. We also reported that the interaction between BAG6 and EP300 occurs in the cytoplasm rather than the nucleus. Moreover, during starvation, EP300 is transported to the nucleus in a BAG6-dependent manner. We concluded that BAG6 regulates autophagy by controlling the localization of EP300 and its accessibility to nuclear (TRP53) and cytoplasmic (ATGs) substrates.
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Salwa
S
Sebti
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Christine
C
Prébois
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Esther
E
Pérez-Gracia
Institut Necker Enfants-Malades; Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1151; Paris, France; CNRS UMR 8243; Paris, France; Université Paris Descartes-Sorbonne Paris Cité; Paris, France.
Chantal
C
Bauvy
Service d'Hématologie; Immunologie et Thérapie Cellulaire; CHU de Rennes; Hôpital Pontchaillou; Rennes, France.
Fabienne
F
Desmots
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Nelly
N
Pirot
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Céline
C
Gongora
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Anne-Sophie
AS
Bach
Department of Biological Sciences; University of Windsor; Windsor, Ontario CA.
Andrew V
AV
Hubberstey
Laboratory of Experimental Hemato-Oncology; Centre de Recherche Public-Santé; Luxembourg, Luxembourg.
Valérie
V
Palissot
Laboratory of Experimental Hemato-Oncology; Centre de Recherche Public-Santé; Luxembourg, Luxembourg.
Guy
G
Berchem
Institut Necker Enfants-Malades; Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1151; Paris, France; CNRS UMR 8243; Paris, France; Université Paris Descartes-Sorbonne Paris Cité; Paris, France.
Patrice
P
Codogno
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Laetitia K
LK
Linares
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Emmanuelle
E
Liaudet-Coopman
Institut de Recherche en Cancérologie de Montpellier; Montpellier, France; Institut National de la Santé et de la Recherche Médicale U896; Montpellier, France; Université Montpellier 1; Montpellier, France; Institut Régional du Cancer Montpellier; Montpellier, France.
Sophie
S
Pattingre
D000107:Acetylation; D000818:Animals; D001343:Autophagy; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D021381:Protein Transport; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C484266:Bag6 protein, mouse; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse
ATG; BAT3; acetylation; autophagy; nucleocytoplasmic shuttling; p53