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

Area of Science:

• Cell Biology
• Molecular Biology
• Autophagy Research

Background:

• Autophagy is a vital cellular process for degrading damaged components.
• The protein EP300/p300 plays a role in acetylation, a key post-translational modification.
• BCL2-associated athanogene 6 (BAG6) has been implicated in cellular stress responses.

Purpose of the Study:

• To elucidate the role of BAG6 in regulating autophagy.
• To investigate the mechanism by which BAG6 influences EP300 activity and substrate acetylation.
• To determine BAG6's involvement in the localization of EP300.

Main Methods:

• Utilized mouse models (E18.5 bag6(-/-) embryos) and mouse embryonic fibroblasts (MEFs).
• Analyzed protein acetylation levels of TRP53 and autophagy-related (ATG) proteins (ATG5, ATG7, LC3-I).
• Investigated the subcellular localization of EP300 in the presence and absence of BAG6.

Main Results:

• BAG6 is essential for both basal and starvation-induced autophagy.
• BAG6 modulates EP300-dependent acetylation of TRP53 and ATG proteins.
• BAG6 regulates the nuclear localization of EP300, impacting its access to nuclear and cytoplasmic substrates.

Conclusions:

• BAG6 controls autophagy by regulating EP300 localization and substrate accessibility.
• BAG6's interaction with EP300 in the cytoplasm is critical for starvation-induced nuclear transport of EP300.
• Dysregulation of BAG6 impairs autophagy through aberrant protein acetylation and EP300 mislocalization.