title: Epigenetic regulation of UBE3A and roles in human neurodevelopmental disorders.
abstract: The E3 ubiquitin ligase UBE3A, also known as E6-AP, has a multitude of ascribed functions and targets relevant to human health and disease. Epigenetic regulation of the UBE3A gene by parentally imprinted noncoding transcription within human chromosome 15q11.2-q13.3 is responsible for the maternal-specific effects of 15q11.2-q13.3 deletion or duplication disorders. Here, we review the evidence for diverse and emerging roles for UBE3A in the proteasome, synapse and nucleus in regulating protein stability and transcription as well as the current mechanistic understanding of UBE3A imprinting in neurons. Angelman and Dup15q syndromes as well as experimental models of these neurodevelopmental disorders are highlighted as improving understanding of UBE3A and its complex regulation for improving therapeutic strategies.
authors.affiliation: Medical Microbiology & Immunology, Genome Center & MIND Institute, University of California, Davis, CA 95616, USA.
authors.forename: Janine M
authors.initials: JM
authors.lastname: LaSalle
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.|Department of Neurology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Reiter
authors.affiliation: Department of Genetics & Developmental Biology & Stem Cell Institute, University of Connecticut, Farmington, CT 06030, USA.
authors.forename: Stormy J
authors.initials: SJ
authors.lastname: Chamberlain
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D059748:Proteolysis; D013569:Synapses / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D014314:Trisomy / Q000235:genetics* / Q000473:pathology; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
chemical_list: D025801:Ubiquitin; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex
keywords: Angelman syndrome; Dup15q syndrome; imprinting; neurodevelopment; proteosome; ubiquitin