ArticleThe Journal of biological chemistry2011
Quantitative cell-based protein degradation assays to identify and classify drugs that target the ubiquitin-proteasome system.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 65 citations in OpenAlex.
- Kinesin-1 mediates proper ER folding of the CaEMBO reports · 2024Article
- Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors.Communications chemistry · 2024Article
- VCF1 is a p97/VCP cofactor promoting recognition of ubiquitylated p97-UFD1-NPL4 substrates.Nature communications · 2024Article
- Optimization of 1,2,4-Triazole-Based p97 Inhibitors for the Treatment of Cancer.ACS medicinal chemistry letters · 2023Article
- The Coming of Age of AI/ML in Drug Discovery, Development, Clinical Testing, and Manufacturing: The FDA Perspectives.Drug design, development and therapy · 2023Article
- Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance.Nature communications · 2022Article
- K27-linked ubiquitylation promotes p97 substrate processing and is essential for cell proliferation.The EMBO journal · 2022Article
- Conserved L464 in p97 D1-D2 linker is critical for p97 cofactor regulated ATPase activity.The Biochemical journal · 2021Article
- Mixed Lineage Kinase 3 phosphorylates prolyl-isomerase PIN1 and potentiates GLI1 signaling in pancreatic cancer development.Cancer letters · 2021Article
- A covalent p97/VCP ATPase inhibitor can overcome resistance to CB-5083 and NMS-873 in colorectal cancer cells.European journal of medicinal chemistry · 2021Article
- Reporter-Based Screens for the Ubiquitin/Proteasome System.Frontiers in chemistry · 2020Review
- A Practical Review of Proteasome Pharmacology.Pharmacological reviews · 2019Review
- Structural Basis of p97 Inhibition by the Site-Selective Anticancer Compound CB-5083.Molecular pharmacology · 2019Article
- Adapted ATPase domain communication overcomes the cytotoxicity of p97 inhibitors.The Journal of biological chemistry · 2018Article
- Epidithiodiketopiperazines Inhibit Protein Degradation by Targeting Proteasome Deubiquitinase Rpn11.Cell chemical biology · 2018Article
- Emerging Cancer Therapeutic Targets in Protein Homeostasis.The AAPS journal · 2018Article
- Article
- Arsenic Compromises Both p97 and Proteasome Functions.Chemical research in toxicology · 2017Article
- Capzimin is a potent and specific inhibitor of proteasome isopeptidase Rpn11.Nature chemical biology · 2017Article
- Reversible phosphorylation of the 26S proteasome.Protein & cell · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
We have generated a set of dual-reporter human cell lines and devised a chase protocol to quantify proteasomal degradation of a ubiquitin fusion degradation (UFD) substrate, a ubiquitin ligase CRL2(VHL) substrate, and a ubiquitin-independent substrate. Well characterized inhibitors that target different aspects of the ubiquitin-proteasome system can be distinguished by their distinctive patterns of substrate stabilization, enabling assignment of test compounds as inhibitors of the proteasome, ubiquitin chain formation or perception, CRL activity, or the UFD-p97 pathway. We confirmed that degradation of the UFD but not the CRL2(VHL) or ubiquitin-independent substrates depends on p97 activity. We optimized our suite of assays to establish conditions suitable for high-throughput screening and then validated their performance by screening against 160 cell-permeable protein kinase inhibitors. This screen identified Syk inhibitor III as an irreversible p97/vasolin containing protein inhibitor (IC(50) = 1.7 μM) that acts through Cys-522 within the D2 ATPase domain. Our work establishes a high-throughput screening-compatible pipeline for identification and classification of small molecules, cDNAs, or siRNAs that target components of the ubiquitin-proteasome system.
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What OpenQuestion holds
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.