BAT3 modulates p300-dependent acetylation of p53 and autophagy-related protein 7 (ATG7) during autophagy

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

Research output: Contribution to journalArticle

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4115-4120
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number11
DOIs
StatePublished - Mar 18 2014

Keywords

  • Degradation
  • Nucleo-cytoplasmic shuttling
  • Signalisation

ASJC Scopus subject areas

  • General

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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., Berchemk, G., Codogno, P., Linares, L. K., Liaudet-Coopman, E., & Pattingre, S. (2014). BAT3 modulates p300-dependent acetylation of p53 and autophagy-related protein 7 (ATG7) during autophagy. Proceedings of the National Academy of Sciences of the United States of America, 111(11), 4115-4120. https://doi.org/10.1073/pnas.1313618111