Study of the eukaryotic translation initiation factor 5A (eIF5A) in mammals

Abstract

The eukaryotic translation initiation factor 5A (eIF5A) protein is highly conserved, been produced by archaea and eukaryotes. This factor possesses a particular amino acid residue named hypusine that is not found in others proteins. The hypusine is essential for its activity and is formed by a post translational modification, using spermidine as substrate, called hypusination. The eIF5A protein has been involved with the translation process; however its precise function remains unknown. Some studies shown that eIF5A has important role in cell proliferation control and HIV-1 replication by acting as a cofactor of the viral protein Rev. In the present project is being proposed to insert eIF5A in biochemical and physiological context of the mammals. To this end, we propose to characterize the signalling pathways that modulate the different points that control eIF5A expression and its hypusination in response to the action of hormones with anabolic or catabolic effect on protein metabolism. Unlike other factors that control the translation process there is no connection between eIF5A and the endocrine system. Experiments are being proposed to characterize the dipeptides a - (g-aminobutyryl)-hypusine and a - (b-alanyl)-hypusine which are formed from the amino acid hypusine. These dipeptides were found in the brain of mammals, but there are no information about their functions and biosynthetic pathways. Regarding the dipeptide a - (g-aminobutyryl)-hypusine, the fact that hypusine be linked to the inhibitory neurotransmitter more representative of the central nervous system, GABA. Finally, we will characterize a human isoform of eIF5A protein (isoform A) that has 30 additional amino acid residues in its N-terminal extremity. To date, there is no functional information on this isoform. (AU)