BAG6/BAT3 modulates autophagy by affecting EP300/p300 intracellular localization

Salwa Sebti (1) , C. Prebois (1) , E. Perez-Gracia (1) , C. Bauvy (2) , F. Desmots (3) , Nelly Pirot (1, 4) , Celine Gongora (1) , Anne-Sophie Bach (1) , A. V. Hubberstey , V. Palissot , G. Berchem , P. Codogno (5, 2) , Laetitia K. Linares (1) , Emmanuelle Liaudet-Coopman (1) , Sophie Pattingre (1)

1 IRCM - U896 Inserm - UM1 - Institut de recherche en cancérologie de Montpellier
2 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
3 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
4 ICM - UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle
5 IRIF (UMR_8243) - Institut de Recherche en Informatique Fondamentale

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.

Mots clés: *Autophagy; acetylation; Intracellular Space/*metabolism; Molecular Chaperones/*metabolism; Intracellular Space; ATG; autophagy; Animals; Protein Transport; Models; Biological; Mice; Nuclear Proteins; BAT3; Molecular Chaperones; E1A-Associated p300 Protein; E1A-Associated p300 Protein/*metabolism; Tumor Suppressor Protein p53; Nuclear Proteins/*metabolism; nucleocytoplasmic shuttling; p53; Tumor Suppressor Protein p53/metabolism

Domaines: Cancer; Biologie cellulaire; Interactions cellulaires [q-bio.CB]

Salwa Sebti, C. Prebois, E. Perez-Gracia, C. Bauvy, F. Desmots, et al.. BAG6/BAT3 modulates autophagy by affecting EP300/p300 intracellular localization. Autophagy, 2014, 10 (7), pp.1341--2. ⟨10.4161/auto.28979⟩. ⟨hal-02168070⟩