ArticleThe Journal of biological chemistry2014
The drug diazaborine blocks ribosome biogenesis by inhibiting the AAA-ATPase Drg1.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 63 citations in OpenAlex.
- A selective NVL inhibitor suppresses tumor growth by targeting ribosome biogenesis.Nature chemical biology · 2026Article
- Chaperone condensates buffer the heat shock response against pleiotropic inputs.bioRxiv : the preprint server for biology · 2026Article
- SMPD3 suppresses oligodendroglioma growth via dual autocrine-paracrine roles.Communications biology · 2026Article
- Establishment of an imaging-based screening pipeline for the identification of human ribosome biogenesis inhibitors.BMC biology · 2025Article
- Ribosome biogenesis in plants requires the nuclear envelope and mitochondria localized OPENER complex.Nature communications · 2025Article
- Cryo-EM structure of the AAA+ SPATA5 complex and its role in human cytoplasmic pre-60S maturation.Nature communications · 2025Article
- Activity of Organoboron Compounds against Biofilm-Forming Pathogens.Antibiotics (Basel, Switzerland) · 2024Review
- Ribosome biogenesis and ribosomal proteins in cancer stem cells: a new therapeutic prospect.Molecular biology reports · 2024Review
- The novel ribosome biogenesis inhibitor usnic acid blocks nucleolar pre-60S maturation.Nature communications · 2024Article
- K29-linked free polyubiquitin chains affect ribosome biogenesis and direct ribosomal proteins to the intranuclear quality control compartment.Molecular cell · 2024Article
- Article
- Structural dynamics of AAA + ATPase Drg1 and mechanism of benzo-diazaborine inhibition.Nature communications · 2022Article
- Visualizing maturation factor extraction from the nascent ribosome by the AAA-ATPase Drg1.Nature structural & molecular biology · 2022Article
- Ribosome-Directed Therapies in Cancer.Biomedicines · 2022Review
- Inhibiting C-4 Methyl Sterol Oxidase with Novel Diazaborines to Target Fungal Plant Pathogens.ACS chemical biology · 2022Article
- Review
- The Boron Advantage: The Evolution and Diversification of Boron's Applications in Medicinal Chemistry.Pharmaceuticals (Basel, Switzerland) · 2022Review
- In situ cryo-electron tomography reveals gradient organization of ribosome biogenesis in intact nucleoli.Nature communications · 2021Article
- Hsf1 activation by proteotoxic stress requires concurrent protein synthesis.Molecular biology of the cell · 2021Article
- Structural basis for inhibition of the AAA-ATPase Drg1 by diazaborine.Nature communications · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
The drug diazaborine is the only known inhibitor of ribosome biogenesis and specifically blocks large subunit formation in eukaryotic cells. However, the target of this drug and the mechanism of inhibition were unknown. Here we identify the AAA-ATPase Drg1 as a target of diazaborine. Inhibitor binding into the second AAA domain of Drg1 requires ATP loading and results in inhibition of ATP hydrolysis in this site. As a consequence the physiological activity of Drg1, i.e. the release of Rlp24 from pre-60S particles, is blocked, and further progression of cytoplasmic preribosome maturation is prevented. Our results identify the first target of an inhibitor of ribosome biogenesis and provide the mechanism of inhibition of a key step in large ribosomal subunit formation.
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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.