ArticleNature communications2014
The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 96 citations in OpenAlex.
- ZnF-UBP domains regulate deubiquitinase activity by relieving ubiquitin product inhibition.Nature communications · 2026Article
- Structural insights into ubiquitin recognition by USP15 revealed through a covalent activity-based probe.Communications biology · 2026Article
- Systematic discovery of motif-based interactions of the auxiliary domains of USP family deubiquitinases.Nature communications · 2026Article
- USP4 modulates ZBP1 ubiquitination to regulate microglial PANoptosis and functional outcomes following traumatic brain injury.Cell death and differentiation · 2026Article
- Design, Synthesis, and Evaluation of Selective Ubiquitin-Specific Protease 11 (USP11) Inhibitors.ACS omega · 2025Article
- Structural and functional insights into Ubl domain-mediated regulation of SARS-CoV-2 PLpro.Biology direct · 2025Article
- Chimeric deubiquitinase engineering reveals structural basis for specific inhibition of the mitophagy regulator USP30.Nature structural & molecular biology · 2025Article
- USP7 V517F mutation as a mechanism of inhibitor resistance.Nature communications · 2025Article
- A novel USP4 inhibitor that suppresses colorectal cancer stemness by promoting β-catenin and Twist1 degradation.Journal of translational medicine · 2025Article
- Alternative proteoforms and proteoform-dependent assemblies in humans and plants.Molecular systems biology · 2024Article
- Variety in the USP deubiquitinase catalytic mechanism.Life science alliance · 2024Article
- What Strengthens Protein-Protein Interactions: Analysis and Applications of Residue Correlation Networks.Journal of molecular biology · 2023Article
- Structural and functional characterization of USP47 reveals a hot spot for inhibitor design.Communications biology · 2023Article
- Ubiquitin Engineering for Interrogating the Ubiquitin-Proteasome System and Novel Therapeutic Strategies.Cells · 2023Review
- USP35 dimer prevents its degradation by E3 ligase CHIP through auto-deubiquitinating activity.Cellular and molecular life sciences : CMLS · 2023Article
- A review of deubiquitinases and thier roles in tumorigenesis and development.Frontiers in bioengineering and biotechnology · 2023Review
- The Role of Deubiquitinating Enzyme in Head and Neck Squamous Cell Carcinoma.International journal of molecular sciences · 2022Review
- Cryo-EM reveals a mechanism of USP1 inhibition through a cryptic binding site.Science advances · 2022Article
- Binding of Vialinin A andMolecules (Basel, Switzerland) · 2022Article
- Identification of an autoinhibitory, mitophagy-inducing peptide derived from the transmembrane domain of USP30.Autophagy · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ubiquitin-specific protease USP4 is emerging as an important regulator of cellular pathways, including the TGF-β response, NF-κB signalling and splicing, with possible roles in cancer. Here we show that USP4 has its catalytic triad arranged in a productive conformation. Nevertheless, it requires its N-terminal DUSP-Ubl domain to achieve full catalytic turnover. Pre-steady-state kinetics measurements reveal that USP4 catalytic domain activity is strongly inhibited by slow dissociation of ubiquitin after substrate hydrolysis. The DUSP-Ubl domain is able to enhance ubiquitin dissociation, hence promoting efficient turnover. In a mechanism that requires all USP4 domains, binding of the DUSP-Ubl domain promotes a change of a switching loop near the active site. This 'allosteric regulation of product discharge' provides a novel way of regulating deubiquitinating enzymes that may have relevance for other enzyme classes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.