ArticleBMC genomics2009
Genome-wide loss-of-function analysis of deubiquitylating enzymes for zebrafish development.
Article in BMC genomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Population Structure and Local Adaptation ofAnimals : an open access journal from MDPI · 2026Article
- Otubain deubiquitinases: Multi-layered regulators of cell fate, development, and stress responses across kingdoms.iScience · 2026Review
- Genetic basis of latitudinal variation in vertebral number in the Oryzias latipes species complex.Zoological letters · 2025Article
- The Deubiquitinating Enzyme USP48 Interacts with the Retinal Degeneration-Associated Proteins UNC119a and ARL3.International journal of molecular sciences · 2022Article
- Ubiquitin Specific Protease USP48 Destabilizes NF-κB/p65 in Retinal Pigment Epithelium Cells.International journal of molecular sciences · 2022Article
- IL-33 enhances Jagged1 mediated NOTCH1 intracellular domain (NICD) deubiquitination and pathological angiogenesis in proliferative retinopathy.Communications biology · 2022Article
- Cezanne is a critical regulator of pathological arterial remodelling by targeting β-catenin signalling.Cardiovascular research · 2022Article
- MiR-103a-3p Promotes Zika Virus Replication by Targeting OTU Deubiquitinase 4 to Activate p38 Mitogen-Activated Protein Kinase Signaling Pathway.Frontiers in microbiology · 2022Article
- The role of USP7 in the Shoc2-ERK1/2 signaling axis and Noonan-like syndrome with loose anagen hair.Journal of cell science · 2021Article
- The Multifaceted Roles of USP15 in Signal Transduction.International journal of molecular sciences · 2021Review
- Deubiquitylases in developmental ubiquitin signaling and congenital diseases.Cell death and differentiation · 2021Review
- Spotlight on USP4: Structure, Function, and Regulation.Frontiers in cell and developmental biology · 2021Review
- NUMB enhances Notch signaling by repressing ubiquitination of NOTCH1 intracellular domain.Journal of molecular cell biology · 2020Article
- Expression of deubiquitinating enzyme genes in the developing mammal retina.Molecular vision · 2019Article
- Induction of OTUD4 by viral infection promotes antiviral responses through deubiquitinating and stabilizing MAVS.Cell research · 2019Article
- USP4 inhibits SMAD4 monoubiquitination and promotes activin and BMP signaling.The EMBO journal · 2017Article
- Expression Atlas of the Deubiquitinating Enzymes in the Adult Mouse Retina, Their Evolutionary Diversification and Phenotypic Roles.PloS one · 2016Article
- Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish.Developmental cell · 2015Article
- Fine-tuning the ubiquitin code at DNA double-strand breaks: deubiquitinating enzymes at work.Frontiers in genetics · 2015Review
- The emerging roles of deubiquitylating enzymes (DUBs) in the TGFβ and BMP pathways.Cellular signalling · 2014Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDeconjugation of ubiquitin and/or ubiquitin-like modified protein substrates is essential to modulate protein-protein interactions and, thus, signaling processes in cells. Although deubiquitylating (deubiquitinating) enzymes (DUBs) play a key role in this process, however, their function and regulation remain insufficiently understood. The "loss-of-function" phenotype studies can provide important information to elucidate the gene function, and zebrafish is an excellent model for this goal.
resultsFrom an in silico genome-wide search, we found more than 90 putative DUBs encoded in the zebrafish genome belonging to six different subclasses. Out of them, 85 from five classical subclasses have been tested with morpholino (MO) knockdown experiments and 57 of them were found to be important in early development of zebrafish. These DUB morphants resulted in a complex and pleiotropic phenotype that, regardless of gene target, always affected the notochord. Based on the huC neuronal marker expression, we grouped them into five sets (groups I to V). Group I DUBs (otud7b, uchl3 and bap1) appear to be involved in the Notch signaling pathway based on the neuronal hyperplasia, while group IV DUBs (otud4, usp5, usp15 and usp25) play a critical role in dorsoventral patterning through the BMP pathway.
conclusionWe have identified an exhaustive list of genes in the zebrafish genome belonging to the five established classes of DUBs. Additionally, we performed the corresponding MO knockdown experiments in zebrafish as well as functional studies for a subset of the predicted DUB genes. The screen results in this work will stimulate functional follow-up studies of potential DUB genes using the zebrafish model system.
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