ArticleCell chemical biology2018
Epidithiodiketopiperazines Inhibit Protein Degradation by Targeting Proteasome Deubiquitinase Rpn11.
Article in Cell chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Balancing Ubiquitination and Deubiquitination in Apoptotic Protein Stability and Cancer Cell Survival.International journal of molecular sciences · 2026Review
- From concept to application: Exploring the evolution and potential of DUBTAC technology.Acta pharmaceutica Sinica. B · 2026Review
- PSMD14 as a translational target in cancer and beyond: from deubiquitination mechanisms to drug resistance and precision therapy.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Molecular glues that inhibit deubiquitylase activity and inflammatory signaling.Nature structural & molecular biology · 2025Article
- Mechanisms and regulation of substrate degradation by the 26S proteasome.Nature reviews. Molecular cell biology · 2025Review
- Enhancing proteasome activity by NMDAR antagonists explains their therapeutic effect in neurodegenerative and mental diseases.Scientific reports · 2025Article
- Novel drug research and therapeutic strategies targeting tumor metastasis and cancer stem cells.Frontiers in pharmacology · 2025Review
- Molecular glues that inhibit deubiquitylase activity and inflammatory signalling.bioRxiv : the preprint server for biology · 2024Article
- Inhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746.iScience · 2024Article
- Function, mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy.Acta pharmaceutica Sinica. B · 2023Review
- High-Throughput Assay for Characterizing Rpn11 Deubiquitinase Activity.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Epipolythiodioxopiperazine-Based Natural Products: Building Blocks, Biosynthesis and Biological Activities.Chembiochem : a European journal of chemical biology · 2022Review
- Cytotoxic N-Methylpretrichodermamide B Reveals Anticancer Activity and Inhibits P-Glycoprotein in Drug-Resistant Prostate Cancer Cells.Marine drugs · 2022Article
- Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.Biomolecules · 2022Review
- Fungal Secondary Metabolites as Inhibitors of the Ubiquitin-Proteasome System.International journal of molecular sciences · 2021Review
- Machine Learning-Enabled Pipeline for Large-Scale Virtual Drug Screening.Journal of chemical information and modeling · 2021Article
- Proteasome interaction with ubiquitinated substrates: from mechanisms to therapies.The FEBS journal · 2021Review
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors.Cancers · 2021Review
- Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 2 countries.
Funding
Abstract
The 26S proteasome is the major proteolytic machine for breaking down cytosolic and nuclear proteins in eukaryotes. Due to the lack of a suitable assay, it is difficult to measure routinely and quantitatively the breakdown of proteins by the 26S proteasome in vitro. In the present study, we developed an assay to monitor proteasome-mediated protein degradation. Using this assay, we discovered that epidithiodiketopiperazine (ETPs) blocked the degradation of our model substrate in vitro. Further characterization revealed that ETPs inhibited proteasome function by targeting the essential proteasomal deubiquitinase Rpn11 (POH1/PSMD14). ETPs also inhibited other JAMM (JAB1/MPN/Mov34 metalloenzyme) proteases such as Csn5 and AMSH. An improved ETP with fewer non-specific effects, SOP11, stabilized a subset of proteasome substrates in cells, induced the unfolded protein response, and led to cell death. SOP11 represents a class of Rpn11 inhibitor and provides an alternative route to develop proteasome inhibitors.
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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.