The Drug Diazaborine Blocks Ribosome Biogenesis by Inhibiting the AAA-ATPase Drg1
| Autor: | Gertrude Zisser, Mathias Loibl, Anna Gungl, Michael Prattes, Lisa Kappel, Claudia Schmidt, Elmar Krieger, Helmut Bergler, Brigitte Pertschy, Isabella Klein |
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| Rok vydání: | 2014 |
| Předmět: |
Boron Compounds
Ribosomal Proteins Cytoplasm Saccharomyces cerevisiae Proteins Preribosome Ribosome biogenesis Saccharomyces cerevisiae Biology Biochemistry Diazaborine Ribosome assembly 03 medical and health sciences chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine Ribosomal protein Large ribosomal subunit Eukaryotic Small Ribosomal Subunit Enzyme Inhibitors Molecular Biology 030304 developmental biology Adenosine Triphosphatases 0303 health sciences Binding Sites Cell Biology Ribosome Subunits Large Eukaryotic AAA proteins Cell biology chemistry Enzymology Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19] 030217 neurology & neurosurgery |
| Zdroj: | Journal of Biological Chemistry, 289, 3913-22 Journal of Biological Chemistry, 289, 7, pp. 3913-22 |
| ISSN: | 0021-9258 |
| Popis: | Contains fulltext : 136109.pdf (Publisher’s version ) (Open Access) 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. |
| Databáze: | OpenAIRE |
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