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Protein Folding Act...
Protein Folding Activity of Ribosomal RNA Is a Selective Target of Two Unrelated Antiprion Drugs
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Tribouillard-Tanvier, Deborah (author)
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- Dos Reis, Suzana (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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Gug, Fabienne (author)
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Voisset, Cecile (author)
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Beringue, Vincent (author)
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Sabate, Raimon (author)
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- Kikovska, Ema (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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Talarek, Nicolas (author)
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Bach, Stephane (author)
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- Huang, Chenhui (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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Desban, Nathalie (author)
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Saupe, Sven J. (author)
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Supattapone, Surachai (author)
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Thuret, Jean-Yves (author)
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Chedin, Stephane (author)
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Vilette, Didier (author)
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Galons, Herve (author)
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- Sanyal, Suparna (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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Blondel, Marc (author)
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(creator_code:org_t)
- 2008-05-14
- 2008
- English.
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 3:5, s. e2174-
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- MEDICINE
- MEDICIN
- NATURAL SCIENCES
- NATURVETENSKAP
Publication and Content Type
- ref (subject category)
- art (subject category)
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PloS one
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- By the author/editor
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Tribouillard-Tan ...
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Dos Reis, Suzana
-
Gug, Fabienne
-
Voisset, Cecile
-
Beringue, Vincen ...
-
Sabate, Raimon
-
show more...
-
Kikovska, Ema
-
Talarek, Nicolas
-
Bach, Stephane
-
Huang, Chenhui
-
Desban, Nathalie
-
Saupe, Sven J.
-
Supattapone, Sur ...
-
Thuret, Jean-Yve ...
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Chedin, Stephane
-
Vilette, Didier
-
Galons, Herve
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Sanyal, Suparna
-
Blondel, Marc
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show less...
- Articles in the publication
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PloS one
- By the university
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Uppsala University