A specificity and toxicity study of GC7 hypusination inhibitor using Saccharomyces cerevisiae model

• Grant number: 14/06270-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2014
• End date: June 30, 2014
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sandro Roberto Valentini
• Grantee: Eleonora Rodrigues Alves Ribeiro
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 10/50044-6 - Study of the role of elF5A in translation elongation, AP.TEM

Abstract

eIF5A is the only protein known to contain the unusual amino acid residue hypusine. This residue is essential for eIF5A function and it is generated by a post-translational modification (hypusination) of a specific lisine residue depending on the polyamine spermidine. The role of GC7 (N1-guanil-1,7- diamin-heptane), an structural analogous of the poliamine spermidine, on growth inhibition of different eukaryotes and tumor cells has already been described by many studies (revisions Preukschas et al. 2012, Lee et al. 2010, Lee et at. 2009). Moreover, it was described the inhibitory activity of hypusination, and consequently eIF5A maturation, in vitro and in vivo by GC7. However, although its inhibitory function of eIF5A activity, GC7 interferes with other cell functions, as stop of translation initiation, cellular stress responses activation and others (Landau et al. 2010). Thus, GC7 does not present specificity and it could be the reason for its toxicity. Then, determining the cellular targets of GC7 could allow us to evaluate its hypusination specificity and the causes of its toxicity.