PUBLICATION
Deubiquitinating Enzymes in Model Systems and Therapy: Redundancy and Compensation Have Implications
- Authors
- Zachariah, S., Gray, D.A.
- ID
- ZDB-PUB-190924-5
- Date
- 2019
- Source
- BioEssays : news and reviews in molecular, cellular and developmental biology 41(11): e1900112 (Review)
- Registered Authors
- Keywords
- RNA interference, compensation, knockout, ohnologue, paralogue, redundancy, ubiquitin-specific protease
- MeSH Terms
-
- Animals
- Deubiquitinating Enzymes/genetics*
- Genome/genetics
- Humans
- Ubiquitin/genetics
- Ubiquitin-Specific Proteases/genetics
- Ubiquitination/genetics
- PubMed
- 31544968 Full text @ Bioessays
Citation
Zachariah, S., Gray, D.A. (2019) Deubiquitinating Enzymes in Model Systems and Therapy: Redundancy and Compensation Have Implications. BioEssays : news and reviews in molecular, cellular and developmental biology. 41(11):e1900112.
Abstract
The multiplicity of deubiquitinating enzymes (DUBs) encoded by vertebrate genomes is partly attributable to whole genome duplication events that occurred early in chordate evolution. By surveying the literature for the largest family of DUBs (the ubiquitin-specific proteases), extensive functional redundancy for duplicated genes has been confirmed as opposed to singletons. Dramatically conflicting results have been reported for loss of function studies conducted through RNA interference as opposed to inactivating mutations, but the contradictory findings can be reconciled by a recently proposed compensatory mechanism involving nonsense-mediated RNA degradation. Duplicated genes are often inactivated to become pseudogenes, and it is proposed that such is the fate of the USP15 gene of zebrafish, a commonly used model system. As it is reviewed here, these observations have implications not only for the interpretation of model system phenotypes but also for therapeutic interventions designed to target DUBs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping