HDAC6 mediates the acetylation of TRIM50

The E3 Ubiquitin ligase TRIM50 promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through HDAC6 interaction, a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. In this report we showed that TRIM50 is a target of HDAC6 with Lys-372 as a critical residue for acetylation. We identified p300 and PCAF as two TRIM50 acetyltransferases and we further showed that a balance between ubiquitination and acetylation regulates TRIM50 degradation. •TRIM50 is acetylated in K372 residue.•HDAC6 drives the TRIM50 deacetylation.•PCAF and p300 are the two TRIM50 acetylases.•TRIM50 acetylation antagonizes with its ubiquitination.•The C-Terminal TRIM50 domain is essential for TRIM50 nucleus-cytosol shuttle.