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Protein folding activity of ribosomal rna is a selective target of two unrelated antiprion drugs

  • Tribouillard-Tanvier, Déborah INSERM U613, Brest, France - Univ Brest, Faculté de Médecine et des Sciences de la Santé, UMR-S613, Brest, France - Etablissement Français du Sang (EFS) Bretagne, Brest, France - CHU Brest, Hop Morvan, Laboratoire de Génétique Moléculaire, Brest, France - CNRS UPS2682, Station Biologique, Protein Phosphorylation & Disease Laboratory, Roscoff, France
  • Reis, Suzana Dos Institute of Cell and Molecular Biology, Uppsala University, Sweden
  • Gug, Fabienne INSERM U648, Laboratoire de Chimie Organique 2, Université Paris Descartes, France
  • Voisset, Cécile INSERM U613, Brest, France - Univ Brest, Faculté de Médecine et des Sciences de la Santé, UMR-S613, Brest, France - Etablissement Français du Sang (EFS) Bretagne, Brest, France - CHU Brest, Hop Morvan, Laboratoire de Génétique Moléculaire, Brest, France
  • Béringue, Vincent Institut National de la Recherche Agronomique (INRA), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France
  • Sabate, Raimon Laboratoire de Génétique Moléculaire des Champignons, IBGC UMR CNRS 5095, Université de Bordeaux 2, France
  • Kikovska, Ema Institute of Cell and Molecular Biology, Uppsala University, Sweden
  • Talarek, Nicolas Department of Medicine/Biochemistry, University of Fribourg, Switzerland
  • Bach, Stéphane CNRS UPS2682, Station Biologique, Protein Phosphorylation & Disease Laboratory, Roscoff, France
  • Huang, Chenhui Institute of Cell and Molecular Biology, Uppsala University, Sweden
  • Desban, Nathalie CNRS UPS2682, Station Biologique, Protein Phosphorylation & Disease Laboratory, Roscoff, France
  • Saupe, Sven J. Laboratoire de Génétique Moléculaire des Champignons, IBGC UMR CNRS 5095, Université de Bordeaux 2, France
  • Supattapone, Surachai Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA - Department of Biochemistry, Dartmouth Medical School, Hanover, New Hampshire, USA
  • Thuret, Jean-Yves CEA, iBiTec-S, Gif- sur-Yvette, France
  • Chédin, Stéphane CEA, iBiTec-S, Gif- sur-Yvette, France
  • Vilette, Didier Institut National de la Recherche Agronomique (INRA), UR892, Virologie Immunologie Moléculaires, Jouy-en-Josas, France
  • Galons, Hervé INSERM U648, Laboratoire de Chimie Organique 2, Université Paris Descartes, France
  • Sanyal, Suparna Institute of Cell and Molecular Biology, Uppsala University, Sweden
  • Blondel, Marc INSERM U613, Brest, France - Univ Brest, Faculté de Médecine et des Sciences de la Santé, UMR-S613, Brest, France - Etablissement Français du Sang (EFS) Bretagne, Brest, France - CHU Brest, Hop Morvan, Laboratoire de Génétique Moléculaire, Brest, France
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    14.05.2008
Published in:
  • PLoS ONE. - 2008, vol. 3, no. 5, p. e2174
English Background: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases.Methodology/Principal Findings: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome.Conclusion/Significance: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/301613
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