ArticleMolecular cell2015
Mechanism of UCH-L5 activation and inhibition by DEUBAD domains in RPN13 and INO80G.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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82 citing papers in PubMed, 121 citations in OpenAlex.
- Positive cytoplasmic UCHL5 tumor expression in gastric cancer is linked to improved prognosis.PloS one · 2018Trial
- Structures of dynamic interactors at native proteasomes by PhIX-MS and cryo-electron microscopy.Molecular cell · 2026Article
- Identification of E3 Ubiquitin Ligases Associated with Survival in Soft Tissue Sarcomas.International journal of molecular sciences · 2026Article
- Substrate biasing in UCHL5 proteoforms.bioRxiv : the preprint server for biology · 2026Article
- Allosteric network of dynamic coupling within BAP1-UCH revealed by methyl NMR.Nature communications · 2026Article
- The Potential Role of Deubiquitinating Enzymes (DUBs) in Male Fertility.Biomolecules · 2026Review
- In-situ cross-linking mass spectrometry reveals compartment-specific proteasomal interactions and structural heterogeneity.Nature communications · 2025Article
- Internal Ubiquitin Electrophiles for Covalent Trapping and Inhibition of Deubiquitinases.Chembiochem : a European journal of chemical biology · 2025Article
- Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome.Nature communications · 2025Article
- NMR-Guided Studies to Establish the Binding Interaction between a Peptoid and Protein.Journal of the American Chemical Society · 2025Article
- Bromodomain proteins IBD1 and IBD2 link histone acetylation to SWR1- and INO80-mediated H2A.Z regulation in Tetrahymena.Epigenetics & chromatin · 2025Article
- GAMT facilitates tumor progression via inhibiting p53 in clear cell renal cell carcinoma.Biology direct · 2025Article
- Prediction of Disordered Linkers Using APOD.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A closer look at the role of deubiquitinating enzymes in the Hypoxia Inducible Factor pathway.Biochemical Society transactions · 2024Review
- Proteasome associated function of UCH37 is evolutionarily conserved in Plasmodium parasites.Scientific reports · 2024Article
- The Structural Role of RPN10 in the 26S Proteasome and an RPN2-Binding Residue on RPN13 Are Functionally Important in Arabidopsis.International journal of molecular sciences · 2024Article
- Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them.American journal of cancer research · 2024Review
- Identification and validation of seed dormancy loci and candidate genes and construction of regulatory networks by WGCNA in maize introgression lines.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2023Article
- Native Semisynthesis of Isopeptide-Linked Substrates for Specificity Analysis of Deubiquitinases and Ubl Proteases.Journal of the American Chemical Society · 2023Article
- Structural basis of histone H2A lysine 119 deubiquitination by Polycomb repressive deubiquitinase BAP1/ASXL1.Science advances · 2023Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deubiquitinating enzymes (DUBs) control vital processes in eukaryotes by hydrolyzing ubiquitin adducts. Their activities are tightly regulated, but the mechanisms remain elusive. In particular, the DUB UCH-L5 can be either activated or inhibited by conserved regulatory proteins RPN13 and INO80G, respectively. Here we show how the DEUBAD domain in RPN13 activates UCH-L5 by positioning its C-terminal ULD domain and crossover loop to promote substrate binding and catalysis. The related DEUBAD domain in INO80G inhibits UCH-L5 by exploiting similar structural elements in UCH-L5 to promote a radically different conformation, and employs molecular mimicry to block ubiquitin docking. In this process, large conformational changes create small but highly specific interfaces that mediate activity modulation of UCH-L5 by altering the affinity for substrates. Our results establish how related domains can exploit enzyme conformational plasticity to allosterically regulate DUB activity. These allosteric sites may present novel insights for pharmaceutical intervention in DUB 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.