Mini Review ARTICLE
UBE3A: an E3 ubiquitin ligase with genome-wide impact in neurodevelopmental disease
- 1University of California, Davis, United States
UBE3A is an E3 ubiquitin ligase encoded by an imprinted gene whose maternal deletion or duplication leads to distinct neurodevelopment disorders Angelman and Dup15q syndromes. Despite the known genetic basis of disease, how changes in copy number of a ubiquitin ligase gene can have widespread impact in early brain development is poorly understood. Previous studies have identified a wide array of UBE3A functions, interaction partners, and ubiquitin targets, but no central pathway fully explains its critical role in neurodevelopment. Here, we review recent UBE3A studies that have begun to investigate mechanistic, cellular pathways and the genome-wide impacts of alterations in UBE3A expression levels. These studies have revealed that UBE3A is a multifunctional protein with important nuclear and cytoplasmic regulatory functions that impact proteasome function, Wnt signaling, circadian rhythms, imprinted gene networks, and chromatin. Synaptic functions of UBE3A interact with light exposures and mTOR signaling and are most critical in GABAergic neurons. Understanding the genome-wide influences of UBE3A will enable future studies to more directly explore the role UBE3A plays in early brain development and ultimately lead to identification of key therapeutic targets for UBE3A-related neurodevelopmental disorders.
Keywords: neurodevelopment, Parental imprinting, human genetics and genomics, synapes, Angelman Syndrome, Autism (ASD)
Received: 18 Sep 2018;
Accepted: 05 Dec 2018.
Edited by:Urs Albrecht, Université de Fribourg, Switzerland
Reviewed by:Dominic Landgraf, Ludwig Maximilian University of Munich, Germany
Toru Takumi, RIKEN Brain Science Institute (BSI), Japan
Copyright: © 2018 Lopez, Segal and LaSalle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Janine M. LaSalle, University of California, Davis, Davis, United States, firstname.lastname@example.org