ArticleJournal of structural biology2016
A conserved two-step binding for the UAF1 regulator to the USP12 deubiquitinating enzyme.
Article in Journal of structural biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Disrupting the USP1-UAF1 deubiquitinase complex: a master regulator of replication stress and frontier target in cancer therapy.Medical oncology (Northwood, London, England) · 2026Review
- USP1 inhibition: A journey from target discovery to clinical translation.Pharmacology & therapeutics · 2025Review
- The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation.EMBO reports · 2024Article
- Structural and Biochemical Insights into the Mechanism of Action of the Clinical USP1 Inhibitor, KSQ-4279.Journal of medicinal chemistry · 2024Article
- The USP46 deubiquitylase complex increases Wingless/Wnt signaling strength by stabilizing Arrow/LRP6.Nature communications · 2023Article
- Cryo-EM reveals a mechanism of USP1 inhibition through a cryptic binding site.Science advances · 2022Article
- Deubiquitinases in cell death and inflammation.The Biochemical journal · 2022Review
- Insert L1 is a central hub for allosteric regulation of USP1 activity.EMBO reports · 2021Article
- Structural basis of FANCD2 deubiquitination by USP1-UAF1.Nature structural & molecular biology · 2021Article
- Deubiquitylating enzymes in neuronal health and disease.Cell death & disease · 2021Review
- Molecular Mechanisms of DUBs Regulation in Signaling and Disease.International journal of molecular sciences · 2021Review
- The WD40-repeat protein WDR-48 promotes the stability of the deubiquitinating enzyme USP-46 by inhibiting its ubiquitination and degradation.The Journal of biological chemistry · 2020Article
- USP22 Interacts with PALB2 and Promotes Chemotherapy Resistance via Homologous Recombination of DNA Double-Strand Breaks.Molecular cancer research : MCR · 2020Article
- Structural insights into the activation of USP46 by WDR48 and WDR20.Cell discovery · 2019Article
- The structure of the deubiquitinase USP15 reveals a misaligned catalytic triad and an open ubiquitin-binding channel.The Journal of biological chemistry · 2018Article
- Article
- The novel anti-androgen candidate galeterone targets deubiquitinating enzymes, USP12 and USP46, to control prostate cancer growth and survival.Oncotarget · 2018Article
- USP48 restrains resection by site-specific cleavage of the BRCA1 ubiquitin mark from H2A.Nature communications · 2018Article
- Article
- Function of the Deubiquitinating Enzyme USP46 in the Nervous System and Its Regulation by WD40-Repeat Proteins.Frontiers in synaptic neuroscience · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulation of deubiquitinating enzyme (DUB) activity is an essential step for proper function of cellular ubiquitin signals. UAF1 is a WD40 repeat protein, which binds and activates three important DUBs, USP1, USP12 and USP46. Here, we report the crystal structure of the USP12-Ub/UAF1 complex at a resolution of 2.8Å and of UAF1 at 2.3Å. In the complex we find two potential sites for UAF1 binding, analogous to what was seen in a USP46/UAF1 complex. In line with these observed dual binding states, we show here that USP12/UAF1 complex has 1:2 stoichiometry in solution, with a two-step binding at 4nM and 325nM respectively. Mutagenesis studies show that the fingers sub-domain of USP12 interacts with UAF1 to form the high affinity interface. Our activation studies confirm that the high affinity binding is important for activation while the second UAF1 binding does not affect activation. Nevertheless, we show that this two step binding is conserved in the well-studied USP12 paralog, USP1. Our results highlight the interfaces essential for regulation of USP12 activity and show a conserved second binding of UAF1 which could be important for regulatory functions independent of USP12 activity.
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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.