Epigenetic regulation of UBE3A and roles in human neurodevelopmental disorders

Janine M LaSalle, Lawrence T. Reiter, Stormy J. Chamberlain

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1213-1228
Number of pages16
JournalEpigenomics
Volume7
Issue number7
DOIs
StatePublished - Oct 1 2015

Fingerprint

Angelman Syndrome
Ubiquitin-Protein Ligases
Protein Stability
Human Chromosomes
Proteasome Endopeptidase Complex
Epigenomics
Synapses
Theoretical Models
Neurons
Health
Genes
Therapeutics
Maternal Inheritance
Imprinting (Psychology)
Neurodevelopmental Disorders

Keywords

  • Angelman syndrome
  • Dup15q syndrome
  • imprinting
  • neurodevelopment
  • proteosome
  • ubiquitin

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Epigenetic regulation of UBE3A and roles in human neurodevelopmental disorders. / LaSalle, Janine M; Reiter, Lawrence T.; Chamberlain, Stormy J.

In: Epigenomics, Vol. 7, No. 7, 01.10.2015, p. 1213-1228.

Research output: Contribution to journalArticle

LaSalle, Janine M ; Reiter, Lawrence T. ; Chamberlain, Stormy J. / Epigenetic regulation of UBE3A and roles in human neurodevelopmental disorders. In: Epigenomics. 2015 ; Vol. 7, No. 7. pp. 1213-1228.
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