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

Salwa Sebti, Christine Prébois, Esther Pérez-Gracia, Chantal Bauvy, Fabienne Desmots, Nelly Pirot, Céline Gongora, Anne Sophie Bach, Andrew V. Hubberstey, Valeŕie Palissot, Guy Berchem, Patrice Codogno, Laetitia K. Linares, Emmanuelle Liaudet-Coopman, Sophie Pattingre

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1341-1342
Number of pages2
JournalAutophagy
Volume10
Issue number7
DOIs
StatePublished - Jul 2014
Externally publishedYes

Keywords

  • Acetylation
  • ATG
  • Autophagy
  • BAT3
  • Nucleocytoplasmic shuttling
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Sebti, S., Prébois, C., Pérez-Gracia, E., Bauvy, C., Desmots, F., Pirot, N., Gongora, C., Bach, A. S., Hubberstey, A. V., Palissot, V., Berchem, G., Codogno, P., Linares, L. K., Liaudet-Coopman, E., & Pattingre, S. (2014). BAG6/BAT3 modulates autophagy by affecting EP300/p300 intracellular localization. Autophagy, 10(7), 1341-1342. https://doi.org/10.4161/auto.28979