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Molecular Evolution, Neurodevelopmental Roles and Clinical Significance of HECT-Type UBE3 E3 Ubiquitin Ligases

Authors :
Mateusz C. Ambrozkiewicz
Katherine J. Cuthill
Dermot Harnett
Hiroshi Kawabe
Victor Tarabykin
Source :
Cells, Vol 9, Iss 11, p 2455 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

Protein ubiquitination belongs to the best characterized pathways of protein degradation in the cell; however, our current knowledge on its physiological consequences is just the tip of an iceberg. The divergence of enzymatic executors of ubiquitination led to some 600–700 E3 ubiquitin ligases embedded in the human genome. Notably, mutations in around 13% of these genes are causative of severe neurological diseases. Despite this, molecular and cellular context of ubiquitination remains poorly characterized, especially in the developing brain. In this review article, we summarize recent findings on brain-expressed HECT-type E3 UBE3 ligases and their murine orthologues, comprising Angelman syndrome UBE3A, Kaufman oculocerebrofacial syndrome UBE3B and autism spectrum disorder-associated UBE3C. We summarize evolutionary emergence of three UBE3 genes, the biochemistry of UBE3 enzymes, their biology and clinical relevance in brain disorders. Particularly, we highlight that uninterrupted action of UBE3 ligases is a sine qua non for cortical circuit assembly and higher cognitive functions of the neocortex.

Details

Language :
English
ISSN :
20734409
Volume :
9
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.f22c39ab30334bcdafe9ebd344ce5530
Document Type :
article
Full Text :
https://doi.org/10.3390/cells9112455