BAG6/BAT3 modulates autophagy by affecting EP300/p300 intracellular localization
#MMPMID24852146
Sebti S
; Prébois C
; Pérez-Gracia E
; Bauvy C
; Desmots F
; Pirot N
; Gongora C
; Bach AS
; Hubberstey AV
; Palissot V
; Berchem G
; Codogno P
; Linares LK
; Liaudet-Coopman E
; Pattingre S
Autophagy
2014[Jul]; 10
(7
): 1341-2
PMID24852146
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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.
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