Search of the eIF5A hypusinaton role through the study of high throughput genetic interaction analysis using eIF5A and its modifying enzyme Dys1 mutants

• Grant number: 12/04418-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2012
• End date: August 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Sandro Roberto Valentini
• Grantee: Fabio Carrilho Galvão
• Supervisor: Brenda Jean Andrews
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Toronto (U of T), Canada

Abstract

The translation initiation factor 5A (eIF5A) is highly conserved from Archaea to mammals and essential for cell viability. eIF5A is the only known protein that contains the essential amino acid hypusine, generated through a posttranslational modification known as hypusination. This modification occurs in two steps: initially the enzyme deoxyhypusine synthase (DYS1) transfers the aminobutyl moiety from the polyamine spermidine to the amino group of a specific eIF5A lysine residue (K51) to form the deoxyhypusine residue. Then, another enzyme, deoxyhypusine hydroxylase (LIA1), performs the hydroxylation of the deoxyhypusine generating the hypusine residue. Although the second step of hypusination (hydroxylation) not be present or may not be essential in all organisms that contains eIF5A, the first step (deoxyhypusination) is present from Archaea to mammals and is essential for eIF5A function. Although eIF5A has recently been described as playing a role in the elongation step of translation, the function of the hypusine residue in this process is still eIF5A obscure. With this aim, it is intended to perform high-throughput analysis of genetic interactions involving eIF5A and Dys1, through an arrangements system of knockout collection of Saccharomyces cerevisiae, which may contribute significantly in the functional characterization of eIF5A and Dys1 in the translation process. (AU)