ArticleThe Journal of biological chemistry2017
Structure and energetics of pairwise interactions between proteasome subunits RPN2, RPN13, and ubiquitin clarify a substrate recruitment mechanism.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Structures of dynamic interactors at native proteasomes by PhIX-MS and cryo-electron microscopy.Molecular cell · 2026Article
- Discovery of Noninhibitory Macrocyclic Ligands for Protein Tyrosine Phosphatase 1B Using a Function-Based, Iterative Screening Strategy.Journal of the American Chemical Society · 2026Article
- Identification of novel ubiquitin receptors on the 26S proteasome by photo-crosslinking mass spectrometry.The Journal of biological chemistry · 2026Article
- SCaN: A Screening and Characterization Platform for Nanosuspensions Enables In Vivo Delivery of a Crystalline hRpn13ACS pharmacology & translational science · 2026Article
- Identification of novel ubiquitin receptors on the 26S proteasome by photo-crosslinking mass spectrometry.bioRxiv : the preprint server for biology · 2025Article
- Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome.Nature communications · 2025Article
- Exploiting Avidity Effects for the Discovery of Low Affinity Protein-Binding Fragments.Journal of medicinal chemistry · 2025Article
- NMR-Guided Studies to Establish the Binding Interaction between a Peptoid and Protein.Journal of the American Chemical Society · 2025Article
- An adaptive peptide-binding site in ubiquitin receptor hRpn13 revealed by structural studies.Nature communications · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Recruitment to the Proteasome Is Necessary but Not Sufficient for Chemically Induced, Ubiquitin-Independent Degradation of Native Proteins.ACS chemical biology · 2024Article
- A structure-based designed small molecule depletes hRpn13Nature communications · 2024Article
- hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF-κB p50.Molecular cell · 2024Article
- Discovery of a non-covalent ligand for Rpn-13, a therapeutic target for hematological cancers.Bioorganic & medicinal chemistry letters · 2023Article
- To Kill or to Be Killed: How Does the Battle between the UPS and Autophagy Maintain the Intracellular Homeostasis in Eukaryotes?International journal of molecular sciences · 2023Review
- Article
- The prognostic value of 19S ATPase proteasome subunits in acute myeloid leukemia and other forms of cancer.Frontiers in medicine · 2023Article
- 19S Proteasome Subunits as Oncogenes and Prognostic Biomarkers in FLT3-Mutated Acute Myeloid Leukemia (AML).International journal of molecular sciences · 2022Article
- Proteasome substrate receptors and their therapeutic potential.Trends in biochemical sciences · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The 26S proteasome is a large cellular assembly that mediates the selective degradation of proteins in the nucleus and cytosol and is an established target for anticancer therapeutics. Protein substrates are typically targeted to the proteasome through modification with a polyubiquitin chain, which can be recognized by several proteasome-associated ubiquitin receptors. One of these receptors, RPN13/ADRM1, is recruited to the proteasome through direct interaction with the large scaffolding protein RPN2 within the 19S regulatory particle. To better understand the interactions between RPN13, RPN2, and ubiquitin, we used human proteins to map the RPN13-binding epitope to the C-terminal 14 residues of RPN2, which, like ubiquitin, binds the N-terminal pleckstrin-like receptor of ubiquitin (PRU) domain of RPN13. We also report the crystal structures of the RPN13 PRU domain in complex with peptides corresponding to the RPN2 C terminus and ubiquitin. Through mutational analysis, we validated the RPN2-binding interface revealed by our structures and quantified binding interactions with surface plasmon resonance and fluorescence polarization. In contrast to a previous report, we find that RPN13 binds ubiquitin with an affinity similar to that of other proteasome-associated ubiquitin receptors and that RPN2, ubiquitin, and the deubiquitylase UCH37 bind to RPN13 with independent energetics. These findings provide a detailed characterization of interactions that are important for proteasome function, indicate ubiquitin affinities that are consistent with the role of RPN13 as a proteasomal ubiquitin receptor, and have major implications for the development of novel anticancer therapeutics.
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Registered trials
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.