ArticleBiochemistry2012
Transient kinetic analysis of USP2-catalyzed deubiquitination reveals a conformational rearrangement in the K48-linked diubiquitin substrate.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- ZnF-UBP domains regulate deubiquitinase activity by relieving ubiquitin product inhibition.Nature communications · 2026Article
- ML364 ameliorates NLRP3-induced inflammatory response.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Photocaged Cell-Permeable Ubiquitin Probe for Temporal Profiling of Deubiquitinating Enzymes.Journal of the American Chemical Society · 2020Article
- TIFAB Regulates USP15-Mediated p53 Signaling during Stressed and Malignant Hematopoiesis.Cell reports · 2020Article
- Crystal structure and activity-based labeling reveal the mechanisms for linkage-specific substrate recognition by deubiquitinase USP9X.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Preferential digestion of PCNA-ubiquitin and p53-ubiquitin linkages by USP7 to remove polyubiquitin chains from substrates.The Journal of biological chemistry · 2019Article
- HIV Protease-Generated Casp8p41, When Bound and Inactivated by Bcl2, Is Degraded by the Proteasome.Journal of virology · 2018Article
- Ubiquitin-specific peptidase 2a (USP2a) deubiquitinates and stabilizes β-catenin.American journal of cancer research · 2018Article
- Steady-state kinetic studies reveal that the anti-cancer target Ubiquitin-Specific Protease 17 (USP17) is a highly efficient deubiquitinating enzyme.Archives of biochemistry and biophysics · 2016Article
- Small Molecule Inhibition of the Ubiquitin-specific Protease USP2 Accelerates cyclin D1 Degradation and Leads to Cell Cycle Arrest in Colorectal Cancer and Mantle Cell Lymphoma Models.The Journal of biological chemistry · 2016Article
- Divergence in Ubiquitin Interaction and Catalysis among the Ubiquitin-Specific Protease Family Deubiquitinating Enzymes.Biochemistry · 2016Article
- USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria.Nature cell biology · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Deubiquitination has emerged as an essential regulatory mechanism of a number of cellular processes. An in-depth understanding of deubiquitinating enzyme (DUB) catalysis, particularly the mode of ubiquitin binding and the individual steps in the DUB catalytic turnover, is imperative for exploiting DUBs for therapeutic intervention. In this work, we present a transient kinetic study of USP2 in hydrolyzing a model substrate Ub-AMC and a physiological substrate K48-linked diubiquitin. We conducted stopped-flow fluorescence analyses of the binding of mono- and diubiquitin to an inactive USP2 mutant and unveiled interesting differences in the binding kinetics between the two substrates. While a simple one-step binding of monoubiquitin to USP2 was observed, a biphasic binding was evident for diubiquitin. We further followed the deubiquitination reaction of Ub-AMC and K48-linked IQF-diubiquitin by USP2 using stopped-flow florescence under a single-turnover condition. Global fitting of the reaction traces revealed differences in the microscopic rate constants between Ub-AMC and the physiological diubiquitin substrate. Our binding and single-turnover data support a conformational rearrangement of the diubiquitin substrate in USP2-catalyzed deubiquitination. This finding is significant given the recent finding that the K48-linked diubiquitin is dynamic in its conformation. Our results provide useful insights into the mechanism of how USP recognizes ubiquitin moieties in a chain structure, which is important for understanding USP catalysis and developing inhibitors against USPs.
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