TY - JOUR
T1 - BAG6/BAT3 modulates autophagy by affecting EP300/p300 intracellular localization
AU - Sebti, Salwa
AU - Prébois, Christine
AU - Pérez-Gracia, Esther
AU - Bauvy, Chantal
AU - Desmots, Fabienne
AU - Pirot, Nelly
AU - Gongora, Céline
AU - Bach, Anne Sophie
AU - Hubberstey, Andrew V.
AU - Palissot, Valeŕie
AU - Berchem, Guy
AU - Codogno, Patrice
AU - Linares, Laetitia K.
AU - Liaudet-Coopman, Emmanuelle
AU - Pattingre, Sophie
N1 - Funding Information:
This work is supported by the Institut National de la Santé et de la Recherche Médicale (CG, PC, LKL, EL-C, and SP), by the ARC foundation (SP), La Ligue Régionale contre Le Cancer (Comités du Gard et de l’Hérault, SP), Cancéropole Grand Sud-Ouest (SP), and the CHEMORES consortium (Tumour Chemotherapy Resistance EU FP6 to EL-C). SS has fellowships from the Fond National de la Recherche Luxembourg (FNR Luxembourg) and La Ligue Nationale contre le Cancer.
PY - 2014/7
Y1 - 2014/7
N2 - 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.
AB - 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.
KW - ATG
KW - Acetylation
KW - Autophagy
KW - BAT3
KW - Nucleocytoplasmic shuttling
KW - p53
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UR - http://www.scopus.com/inward/citedby.url?scp=84903784613&partnerID=8YFLogxK
U2 - 10.4161/auto.28979
DO - 10.4161/auto.28979
M3 - Article
C2 - 24852146
AN - SCOPUS:84903784613
SN - 1554-8627
VL - 10
SP - 1341
EP - 1342
JO - Autophagy
JF - Autophagy
IS - 7
ER -