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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)

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Scientific publications (7)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PEREIRA, KARINA DANIELLE; TAMBORLIN, LETICIA; MENEGUELLO, LETICIA; GOMES DE PROENCA, ANDRE RICARDO; DE PAULA ANDRADE ALMEIDA, ISADORA CRISTINA; LOURENCO, ROGERIO FERREIRA; LUCHESSI, AUGUSTO DUCATI. Alternative Start Codon Connects eIF5A to Mitochondria. Journal of Cellular Physiology, v. 231, n. 12, p. 2682-2689, . (14/01386-2, 13/25263-4, 10/18095-0, 13/20504-3)
COSTA DE FREITAS, RENATA C.; BORTOLIN, RAUL H.; LOPES, MARIANA B.; TAMBORLIN, LETICIA; MENEGUELLO, LETICIA; SILBIGER, VIVIAN N.; HIRATA, ROSARIO D. C.; HIRATA, MARIO H.; LUCHESSI, AUGUSTO D.; LUCHESSI, ANDRE D.. Modulation of miR-26a-5p and miR-15b-5p Exosomal Expression Associated with Clopidogrel-Induced Hepatotoxicity in HepG2 Cells. FRONTIERS IN PHARMACOLOGY, v. 8, . (10/18095-0)
TAMBORLIN, LETICIA; SUMERE, BEATRIZ ROCCHETTI; DE SOUZA, MARIANA CORREA; PESTANA, NATHALIE FORTES; AGUIAR, ANA CAROLINA; EBERLIN, MARCOS NOGUEIRA; SIMABUCO, FERNANDO MOREIRA; ROSTAGNO, MAURICIO ARIEL; LUCHESSI, AUGUSTO DUCATI. Characterization of pomegranate peel extracts obtained using different solvents and their effects on cell cycle and apoptosis in leukemia cells. FOOD SCIENCE & NUTRITION, v. 8, n. 10, . (18/17089-8, 15/18119-0, 19/06951-3, 10/18095-0, 18/14818-9, 17/21914-1, 13/04304-4)
PEREIRA, KARINA D.; TAMBORLIN, LETICIA; DE LIMA, I, TANES; CONSONNI, SILVIO R.; SILVEIRA, LEONARDO R.; LUCHESSI, AUGUSTO D.. Alternative human eIF5A protein isoform plays a critical role in mitochondria. Journal of Cellular Biochemistry, v. 122, n. 5, . (17/21914-1, 13/23620-4, 19/06951-3, 10/18095-0)
GOMES DE PROENCA, ANDRE RICARDO; PEREIRA, KARINA DANIELLE; MENEGUELLO, LETICIA; TAMBORLIN, LETICIA; LUCHESSI, AUGUSTO DUCATI. Insulin action on protein synthesis and its association with eIF5A expression and hypusination. MOLECULAR BIOLOGY REPORTS, v. 46, n. 1, p. 587-596, . (14/27154-0, 10/18095-0, 17/21914-1, 13/23620-4, 13/20504-3)
MENEGUELLO, LETICIA; BARBOSA, NATALIA M.; PEREIRA, KARINA D.; PROENCA, ANDRE R. G.; TAMBORLIN, LETICIA; SIMABUCO, FERNANDO M.; IWAI, LEO K.; ZANELLI, CLESLEI F.; VALENTINI, SANDRO R.; LUCHESSI, AUGUSTO D.. The polyproline-motif of S6K2: eIF5A translational dependence and importance for protein-protein interactions. Journal of Cellular Biochemistry, v. 120, n. 4, p. 6015-6025, . (13/07467-1, 12/13558-7, 10/18095-0)
REZENDE DUARTE, VICTOR HUGO; CRUZ, MARINA SAMPAIO; BERTOLAMI, ADRIANA; HIRATA, MARIO HIROYUKI; CRESPO HIRATA, ROSARIO DOMINGUEZ; LUCHESSI, ANDRE DUCATI; SILBIGER, VIVIAN NOGUEIRA. TREML4 polymorphisms increase the mRNA in blood leukocytes in the progression of atherosclerosis. SCIENTIFIC REPORTS, v. 12, n. 1, p. 9-pg., . (10/18095-0)

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Filed patent(s) as a result of this research project

KIT X-PEI E MÉTODO DE TRANSFECÇÃO CELULAR BR1020160113679 - Universidade Estadual de Campinas (UNICAMP) . Augusto Ducati Luchessi ; Karina Danielle Pereira ; Tavane David Cambiaghi ; Leticia Tamborlin ; Leticia Meneguello ; André Ricardo Gomes De Proença - May 2016, 19

(EN) X-PEI KIT AND CELL TRANSFECTION METHOD PCT/BR2016/000143 - Universidade Estadual de Campinas (UNICAMP) . LUCHESSI, Augusto Ducati ; PEREIRA, Karina Danielle ; CAMIAGHI, Tavane David ; TAMBORLIN, Leticia ; MENEGUELLO, Leticia ; DE PROENÇA, André Ricardo Gomes - December 2016, 15