ArticleProceedings of the National Academy of Sciences of the United States of America2015
Structural characterization of the interaction of Ubp6 with the 26S proteasome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 112 citations in OpenAlex.
- Proteasome activity maintains cell-type-specific gene expression.Cell reports · 2026Article
- Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome.Nature communications · 2025Article
- A kinetic model for USP14 regulated substrate degradation in 26S proteasome.PLoS computational biology · 2025Article
- Spatial mechanisms of quality control during chaperone-mediated assembly of the proteasome.Nature communications · 2025Article
- Dynamic networks connect the USP14 active site region with the proteasome interaction surface.Protein science : a publication of the Protein Society · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Proteotoxic stress and the ubiquitin proteasome system.Seminars in cell & developmental biology · 2024Review
- Wiggle and Shake: Managing and Exploiting Conformational Dynamics during Proteasome Biogenesis.Biomolecules · 2023Review
- FAT10 and NUB1L cooperate to activate the 26S proteasome.Life science alliance · 2023Article
- Proteasome substrate receptors and their therapeutic potential.Trends in biochemical sciences · 2022Review
- DUB-le vision: snapshots of the proteasome during substrate processing.Trends in biochemical sciences · 2022Article
- Article
- Allosteric control of Ubp6 and the proteasome via a bidirectional switch.Nature communications · 2022Article
- Research Progress of DUB Enzyme in Hepatocellular Carcinoma.Frontiers in oncology · 2022Review
- Advances in Proteasome Enhancement by Small Molecules.Biomolecules · 2021Review
- Proteasome interaction with ubiquitinated substrates: from mechanisms to therapies.The FEBS journal · 2021Review
- Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases.International journal of molecular sciences · 2021Review
- Mechanisms That Activate 26S Proteasomes and Enhance Protein Degradation.Biomolecules · 2021Review
- Proteasome in action: substrate degradation by the 26S proteasome.Biochemical Society transactions · 2021Review
- Review
14 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotic cells, the 26S proteasome is responsible for the regulated degradation of intracellular proteins. Several cofactors interact transiently with this large macromolecular machine and modulate its function. The deubiquitylating enzyme ubiquitin C-terminal hydrolase 6 [Ubp6; ubiquitin-specific protease (USP) 14 in mammals] is the most abundant proteasome-interacting protein and has multiple roles in regulating proteasome function. Here, we investigate the structural basis of the interaction between Ubp6 and the 26S proteasome in the presence and absence of the inhibitor ubiquitin aldehyde. To this end we have used single-particle electron cryomicroscopy in combination with cross-linking and mass spectrometry. Ubp6 binds to the regulatory particle non-ATPase (Rpn) 1 via its N-terminal ubiquitin-like domain, whereas its catalytic USP domain is positioned variably. Addition of ubiquitin aldehyde stabilizes the binding of the USP domain in a position where it bridges the proteasome subunits Rpn1 and the regulatory particle triple-A ATPase (Rpt) 1. The USP domain binds to Rpt1 in the immediate vicinity of the Ubp6 active site, which may effect its activation. The catalytic triad is positioned in proximity to the mouth of the ATPase module and to the deubiquitylating enzyme Rpn11, strongly implying their functional linkage. On the proteasome side, binding of Ubp6 favors conformational switching of the 26S proteasome into an intermediate-energy conformational state, in particular upon the addition of ubiquitin aldehyde. This modulation of the conformational space of the 26S proteasome by Ubp6 explains the effects of Ubp6 on the kinetics of proteasomal degradation.
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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.