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Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation

Laboratory for Neurobiology of Psychiatric Disorders, Sagol Department of Neurobiology, University of Haifa, 199 Aba Khoushy Ave., Mt. Carmel, Haifa 3498838, Israel
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Author to whom correspondence should be addressed.
Lilach Simchi and Julia Panov contributed equally to this paper.
J. Clin. Med. 2020, 9(5), 1573; https://doi.org/10.3390/jcm9051573
Received: 5 March 2020 / Revised: 5 May 2020 / Accepted: 17 May 2020 / Published: 22 May 2020
(This article belongs to the Special Issue The Rise of Mitochondria in Medicine)
The UBE3A gene codes for a protein with two known functions, a ubiquitin E3-ligase which catalyzes ubiquitin binding to substrate proteins and a steroid hormone receptor coactivator. UBE3A is most famous for its critical role in neuronal functioning. Lack of UBE3A protein expression leads to Angelman syndrome (AS), while its overexpression is associated with autism. In spite of extensive research, our understanding of UBE3A roles is still limited. We investigated the cellular and molecular effects of Ube3a deletion in mouse embryonic fibroblasts (MEFs) and Angelman syndrome (AS) mouse model hippocampi. Cell cultures of MEFs exhibited enhanced proliferation together with reduced apoptosis when Ube3a was deleted. These findings were supported by transcriptome and proteome analyses. Furthermore, transcriptome analyses revealed alterations in mitochondria-related genes. Moreover, an analysis of adult AS model mice hippocampi also found alterations in the expression of apoptosis- and proliferation-associated genes. Our findings emphasize the role UBE3A plays in regulating proliferation and apoptosis and sheds light into the possible effects UBE3A has on mitochondrial involvement in governing this balance. View Full-Text
Keywords: UBE3A; Angelman syndrome; apoptosis; proliferation; mitochondria; bioinformatics; RNA editing UBE3A; Angelman syndrome; apoptosis; proliferation; mitochondria; bioinformatics; RNA editing
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Simchi, L.; Panov, J.; Morsy, O.; Feuermann, Y.; Kaphzan, H. Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation. J. Clin. Med. 2020, 9, 1573.

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