UBE3A: An E3 Ubiquitin Ligase With Genome-Wide Impact in Neurodevelopmental Disease

Frontiers in Molecular Neuroscience
S Jesse LopezJanine M LaSalle


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 to gain broader insight into how UBE3A affects the developing brain. 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 help uncover its role in early brain development and ultimat...Continue Reading


Feb 1, 1996·Journal of Medical Genetics·A SmithR J Trent
Aug 24, 1999·Molecular and Cellular Biology·K YankulovD L Bentley
Dec 7, 2002·Nature Neuroscience·Hiroki YasudaRobert C Malenka
Nov 9, 2004·Current Opinion in Cell Biology·Maurice Kléber, Lukas Sommer
Oct 28, 2005·Nature·Dieter-Chichung LieFred H Gage
Oct 31, 2006·PLoS Genetics·Robert W RapkinsJennifer A Marshall Graves
Sep 4, 2007·Sleep Medicine·Karine PelcBernard Dan
Jul 5, 2008·Cancer Cell·Francesca BernassolaGerry Melino
Aug 25, 2009·Nature Neuroscience·Tomoko KuwabaraFred H Gage
Nov 10, 2009·Virology·Hava LichtigLevana Sherman
Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·Daphna Zaaroor-RegevAaron Ciechanover
Dec 21, 2010·Nature Neuroscience·Alex BayésSeth G N Grant
Jun 10, 2011·The Journal of Biological Chemistry·Yuan LuJohannes W Hell
Sep 29, 2011·Annual Review of Physiology·John P AdelmanPankaj Sah
Nov 3, 2011·Journal of Intellectual Disability Research : JIDR·S E GoldmanB A Malow
May 31, 2012·Molecular and Cellular Biology·Gustavo Martínez-NoëlPeter M Howley
Jan 4, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sheng MiaoZhi-Qi Xiong
Apr 20, 2014·Molecular Biology of the Cell·Andrew D JacobsonChang-Wei Liu
Sep 24, 2014·Scientific Reports·Chenna R GalivetiTimofey S Rozhdestvensky
Oct 24, 2014·Proceedings. Biological Sciences·Barry G LovegroveDanielle L Levesque
Nov 5, 2014·Nature·Silvia De RubeisJoseph D Buxbaum
Feb 11, 2015·Current Biology : CB·Shu-qun ShiCarl Hirschie Johnson
Mar 20, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jiandong SunXiaoning Bi
Apr 14, 2015·The Journal of Clinical Investigation·Sara Silva-SantosYpe Elgersma
Apr 14, 2015·Nature Neuroscience·Jeremy ValluyGerhard Schratt
May 9, 2015·Genome Research·Yael BaranTuuli Lappalainen
Oct 7, 2015·Frontiers in Neuroscience·Gabrielle L Sell, Seth S Margolis
Nov 21, 2015·Epigenomics·Janine M LaSalleStormy J Chamberlain
Mar 8, 2016·Neuroscience and Biobehavioral Reviews·Alan Packer
Apr 29, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hyojin KimSpencer L Smith
May 14, 2016·Cellular and Molecular Life Sciences : CMLS·Jiandong SunXiaoning Bi
Jun 25, 2016·The Journal of Comparative Neurology·Alain C BuretteRichard J Weinberg
Feb 10, 2017·Oncotarget·Jiandong SunXiaoning Bi
Mar 23, 2017·Frontiers in Cellular Neuroscience·Masaaki Sato
May 19, 2017·Epigenetics & Chromatin·Paul R HillmanScott V Dindot
Sep 20, 2017·Epigenetics : Official Journal of the DNA Methylation Society·S Jesse LopezJanine M LaSalle
Feb 10, 2018·Journal of Molecular Biology·Gustavo Martínez-NoëlPeter M Howley


Dec 24, 2019·Journal of Neuroscience Research·Xin Yang
Jun 14, 2020·International Journal of Molecular Sciences·Julia PanovHanoch Kaphzan
Jun 18, 2020·International Journal of Molecular Sciences·Chuanyin LiRonggui Hu
Jun 18, 2020·Molecular Autism·Alejandro López-TobónGiuseppe Testa
Jan 22, 2021·Autism Research : Official Journal of the International Society for Autism Research·Andie DodgeKevin R Nash
Feb 24, 2020·Neuroscience·Diana C RotaruYpe Elgersma

Related Concepts

Circadian Rhythms
Gene Deletion
Gene Duplication
Physiological Aspects

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Systemic Juvenile Idiopathic Arthritis

Systemic juvenile idiopathic arthritis is a rare rheumatic disease that affects children. Symptoms include joint pain, but also fevers and skin rashes. Here is the latest on this disease.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Central Pontine Myelinolysis

Central Pontine Myelinolysis is a neurologic disorder caused most frequently by rapid correction of hyponatremia and is characterized by demyelination that affects the central portion of the base of the pons. Here is the latest research on this disease.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Pontocerebellar Hypoplasia

Pontocerebellar hypoplasias are a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. Here is the latest research on pontocerebellar hypoplasia.

Cell Atlas Along the Gut-Brain Axis

Profiling cells along the gut-brain axis at the single cell level will provide unique information for each cell type, a three-dimensional map of how cell types work together to form tissues, and insights into how changes in the map underlie health and disease of the GI system and its crosstalk with the brain. Disocver the latest research on single cell analysis of the gut-brain axis here.

Chronic Traumatic Encephalopathy

Chronic Traumatic Encephalopathy (CTE) is a progressive degenerative disease that occurs in individuals that suffer repetitive brain trauma. Discover the latest research on traumatic encephalopathy here.