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

• Grant number: 10/18095-0
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: September 01, 2011
• End date: November 30, 2016
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Augusto Ducati Luchessi
• Grantee: Augusto Ducati Luchessi
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Associated researchers: Beatriz Amaral de Castilho ; Mario Hiroyuki Hirata ; Rui Curi ; Tavane David Cambiaghi ; Vagner Roberto Antunes
• Associated scholarship(s): 13/23620-4 - Functional characterization of the translation factor EIF5A isoform A, BP.DR; 14/01386-2 - The role of eukaryotic translation initiation factor 5A (EIF5A) in the translation of s6ks proteins, BP.IC; 13/25263-4 - Identification and characterization of a homologue of human EIF5A isoform A in mouse, BP.IC

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)

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)

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, DEC 12 2017. (10/18095-0)

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, DEC 2016. (14/01386-2, 13/25263-4, 10/18095-0, 13/20504-3)

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, FEB 2019. (14/27154-0, 10/18095-0, 17/21914-1, 13/23620-4, 13/20504-3)

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, JAN 2021. (17/21914-1, 13/23620-4, 19/06951-3, 10/18095-0)

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, APR 2019. (13/07467-1, 12/13558-7, 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, AUG 2020. (18/17089-8, 15/18119-0, 19/06951-3, 10/18095-0, 18/14818-9, 17/21914-1, 13/04304-4)

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., 2022-11-03. (10/18095-0)

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