AUTHOR=Elu Nagore , Osinalde Nerea , Beaskoetxea Javier , Ramirez Juanma , Lectez Benoit , Aloria Kerman , Rodriguez Jose Antonio , Arizmendi Jesus M. , Mayor Ugo 

TITLE=Detailed Dissection of UBE3A-Mediated DDI1 Ubiquitination

JOURNAL=Frontiers in Physiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.00534

DOI=10.3389/fphys.2019.00534

ISSN=1664-042X

ABSTRACT=<p>The ubiquitin E3 ligase UBE3A has been widely reported to interact with the proteasome, but it is still unclear how this enzyme regulates by ubiquitination the different proteasomal subunits. The proteasome receptor DDI1 has been identified both in <italic>Drosophila</italic> photoreceptor neurons and in human neuroblastoma cells in culture as a direct substrate of UBE3A. Here, we further characterize this regulation, by identifying the UBE3A-dependent ubiquitination sites and ubiquitin chains formed on DDI1. Additionally, we found one deubiquitinating enzyme that is capable of reversing the action of UBE3A on DDI1. The complete characterization of the ubiquitination pathway of an UBE3A substrate is important due to the role of this E3 ligase in rare neurological disorders as Angelman syndrome.</p>