ArticleeLife2022
A cryptic K48 ubiquitin chain binding site on UCH37 is required for its role in proteasomal degradation.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 26 citations in OpenAlex.
- Tied to Work: Topologically Knotted SPOUT Methyltransferases and UCH Deubiquitinases in Cellular Biochemistry.Journal of cellular biochemistry · 2026Review
- mTORC2 Phosphorylation of GSDME-N Drives Cullin4B-Mediated Proteasomal Degradation to Suppress Pyroptosis and Confer Radioresistance in Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DTX3L promotes ovarian cancer progression and cisplatin resistance by activating JAK1/STAT1/OAS3 pathway.Scientific reports · 2026Article
- Internal Ubiquitin Electrophiles for Covalent Trapping and Inhibition of Deubiquitinases.Chembiochem : a European journal of chemical biology · 2025Article
- In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target.Nature communications · 2025Article
- Heterogeneous protein dynamics links to mitochondrial activity, glucose transporter, and ALDH cancer stem cell properties.BMC cancer · 2025Article
- Cytosolic Delivery of Functional Ubiquitin.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Combinatorial ubiquitin code degrades deubiquitylation-protected substrates.Nature communications · 2025Article
- OTUD5 Protects Dopaminergic Neurons by Promoting the Degradation of α-Synuclein in Parkinson's Disease Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Activation and Reactivity of the Deubiquitinylase OTU Cezanne-2 from MD Simulations and QM/MM Calculations.Journal of chemical information and modeling · 2025Article
- VCP/p97-associated proteins are binders and debranching enzymes of K48-K63-branched ubiquitin chains.Nature structural & molecular biology · 2024Article
- Proteasome associated function of UCH37 is evolutionarily conserved in Plasmodium parasites.Scientific reports · 2024Article
- Insect ribosome-rescuer Pelo-Hbs1 complex on sperm surface mediates paternal arbovirus transmission.Nature communications · 2024Article
- Facile Access to Branched Multispecific Proteins.Bioconjugate chemistry · 2024Article
- Reading and Writing the Ubiquitin Code Using Genetic Code Expansion.Chembiochem : a European journal of chemical biology · 2024Review
- The emerging roles of non-canonical ubiquitination in proteostasis and beyond.The Journal of cell biology · 2024Review
- USP15 promotes the progression of papillary thyroid cancer by regulating HMGB1 stability through its deubiquitination.Journal of Cancer · 2024Article
- Uncovering DUB Selectivity through an Ion Mobility-Based Assessment of Ubiquitin Chain Isomers.Analytical chemistry · 2023Article
- The E3 ubiquitin ligase RNF216 contains a linear ubiquitin chain-determining-like domain that functions to regulate dendritic arborization and dendritic spine type in hippocampal neurons.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Degradation by the 26 S proteasome is an intricately regulated process fine tuned by the precise nature of ubiquitin modifications attached to a protein substrate. By debranching ubiquitin chains composed of K48 linkages, the proteasome-associated ubiquitin C-terminal hydrolase UCHL5/UCH37 serves as a positive regulator of protein degradation. How UCH37 achieves specificity for K48 chains is unclear. Here, we use a combination of hydrogen-deuterium mass spectrometry, chemical crosslinking, small-angle X-ray scattering, nuclear magnetic resonance (NMR), molecular docking, and targeted mutagenesis to uncover a cryptic K48 ubiquitin (Ub) chain-specific binding site on the opposite face of UCH37 relative to the canonical S1 (cS1) ubiquitin-binding site. Biochemical assays demonstrate the K48 chain-specific binding site is required for chain debranching and proteasome-mediated degradation of proteins modified with branched chains. Using quantitative proteomics, translation shutoff experiments, and linkage-specific affinity tools, we then identify specific proteins whose degradation depends on the debranching activity of UCH37. Our findings suggest that UCH37 and potentially other DUBs could use more than one S1 site to perform different biochemical functions.
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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.