The UBE2D ubiquitin conjugating enzymes: Potential regulatory hubs in development, disease and evolution
Author(s)
Roman-Trufero, Monica
Dillon, Niall
Type
Journal Article
Abstract
Ubiquitination of cellular proteins plays critical roles in key signalling pathways and in the regulation of protein turnover in eukaryotic cells. E2 ubiquitin conjugating enzymes function as essential intermediates in ubiquitination reactions by acting as ubiquitin donors for the E3 ubiquitin ligase enzymes that confer substrate specificity. The members of the UBE2D family of E2 enzymes are involved in regulating signalling cascades through ubiquitination of target proteins that include receptor tyrosine kinases (RTKs) and components of the Hedgehog, TGFβ and NFκB pathways. UBE2D enzymes also function in transcriptional control by acting as donors for ubiquitination of histone tails by the Polycomb protein Ring1B and the DNA methylation regulator UHRF1 as well as having roles in DNA repair and regulation of the level of the tumour suppressor p53. Here we review the functional roles and mechanisms of regulation of the UBE2D proteins including recent evidence that regulation of the level of UBE2D3 is critical for controlling ubiquitination of specific targets during development. Cellular levels of UBE2D3 have been shown to be regulated by phosphorylation, which affects folding of the protein, reducing its stability. Specific variations in the otherwise highly conserved UBE2D3 protein sequence in amniotes and in a subgroup of teleost fishes, the Acanthomorpha, suggest that the enzyme has had important roles during vertebrate evolution.
Date Issued
2022-12-12
Date Acceptance
2022-11-24
Citation
Frontiers in Cell and Developmental Biology, 2022, 10, pp.1-14
ISSN
2296-634X
Publisher
Frontiers Media
Start Page
1
End Page
14
Journal / Book Title
Frontiers in Cell and Developmental Biology
Volume
10
Copyright Statement
Copyright © 2022 Roman-Trufero and Dillon. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
License URL
Identifier
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000903822800001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=a2bf6146997ec60c407a63945d4e92bb
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Developmental Biology
ubiquitination
UBE2D3
phosphorylation
development
evolution
KAPPA-B-ALPHA
EMBRYONIC LETHALITY
CRYSTAL-STRUCTURE
DNA METHYLATION
S-NITROSYLATION
LIGASE COMPLEX
E2 ENZYMES
CELL-DEATH
E3 LIGASE
HEDGEHOG
Publication Status
Published
Article Number
ARTN 1058751
Date Publish Online
2022-12-12