Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/108511
Title: Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation
Authors: Blondel, S.
Egesipe, A-L
Picardi, P.
Jaskowiak, A-L
Notarnicola, M.
Ragot, J.
Tournois, J.
Le Corf, A.
Brinon, B.
Poydenot, P.
Georges, P.
Navarro, C.
Pitrez, P. R. 
Ferreira, L. 
Bollot, G.
Bauvais, C.
Laustriat, D.
Mejat, A.
De Sandre-Giovannoli, A.
Levy, N.
Bifulco, M.
Peschanski, M.
Nissan, X.
Issue Date: 18-Feb-2016
Publisher: Springer Nature
Project: Institut National de la Santé et de la Recherche Médicale (INSERM) 
National Infrastructure Engineering for Pluripotent and differentiated Stem cells (INGESTEM) 
Humanis 
Evry Val d’Essonne University (UEVE) 
Programa Operacional Factores de Competitividade (FCOMP-01-2014-FEDER-041659) 
Genopole 
Serial title, monograph or event: Cell Death and Disease
Volume: 7
Issue: 2
Abstract: Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by a dramatic appearance of premature aging. HGPS is due to a single-base substitution in exon 11 of the LMNA gene (c.1824C>T) leading to the production of a toxic form of the prelamin A protein called progerin. Because farnesylation process had been shown to control progerin toxicity, in this study we have developed a screening method permitting to identify new pharmacological inhibitors of farnesylation. For this, we have used the unique potential of pluripotent stem cells to have access to an unlimited and relevant biological resource and test 21,608 small molecules. This study identified several compounds, called monoaminopyrimidines, which target two key enzymes of the farnesylation process, farnesyl pyrophosphate synthase and farnesyl transferase, and rescue in vitro phenotypes associated with HGPS. Our results opens up new therapeutic possibilities for the treatment of HGPS by identifying a new family of protein farnesylation inhibitors, and which may also be applicable to cancers and diseases associated with mutations that involve farnesylated proteins.
URI: https://hdl.handle.net/10316/108511
ISSN: 2041-4889
DOI: 10.1038/cddis.2015.374
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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