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Eif5a Interacts Functionally with Eef2 in Yeast Camila A. O. Dias1; Ana Paula B. Gregio1; Danuza Rossi1; Fábio C. Galvão1;

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Formatado: Fonte: Negrito eIF5A interacts functionally with eEF2 in yeast Excluído: ¶ Formatado: Camila A. O. Dias1; Ana Paula B. Gregio1; Danuza Rossi1; Fábio C. Galvão1; Tatiana F. Espaçamento entre linhas: 1,5 linha 1 2 1 1 Excluído: and Watanabe ; Myung H. Park ; Cleslei F. Zanelli ; Sandro R. Valentini physically Formatado: Fonte: 1 Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo Negrito Excluído: ¶ State University – UNESP, Araraquara, Brazil Excluído: l¶ Excluído: ¶ 2 National Institutes of Health, Bethesda, MD, USA Excluído: eukaryotic Excluído: iniation The eukaryotic translation factor eIF5A is highly conserved, essential for cell viability Excluído: analysis and it is the only cellular protein known to contain the essential amino acid hypusine. Excluído: as was observed for an eEF2 eIF5A was originally identified as a translation initiation factor. However, studies mutant and wild type cells demonstrated that depletion of eIF5A causes a significant increase of the ribosome treated with sordarin, [SD1] Comentário: Synt transit time and decrease of polysome run-off, suggesting that eIF5A is involved in the hetic sick? Do you mean like a specific genetic interaction? elongation step of protein synthesis. We have previously shown that the eIF5A Formatado: Fonte: depletion mutant tif51A-3 has a synthetic sick genetic interaction with the dominant Itálico Formatado: Fonte: H699K K56A Itálico negative mutant eft2 of eEF2. Here we use the stable mutant eIF5A to further Formatado: Fonte: analyze the functional interaction with eEF2. The eIF5AK56A mutant is temperature- Itálico, Sobrescrito Excluído: reverted sensitive and show defects in protein synthesis as that observed during eIF5A Excluído: Here, we use depletion. Interestingly, the overproduction of eEF2 improves the cell growth of the the eIF5AK56A and Q22H/L93F K56A K56A eIF5A mutants to eIF5A mutant strain and the polysome profile defect of the eIF5A mutant is investigate the relationship between eIF5A and eEF2. partially complemented by overproduction of eEF2. These data further support the These eIF5A mutants are temperature-sensitive and functional link between eIF5A and eEF2, and future experiments will aim to dissect the show defect in protein mechanism of eIF5A in translation elongation together with eEF2. synthesis as previously observed for eIF5A depletion, but eIF5AK56A and Supported by FAPESP, CNPq and PADC-FCF. eIF5AQ22H/L93F proteins are stable at the restrictive temperature. Their main... [1] Formatado: Inglês (EUA) Excluído: reveal Excluído: for the first... [2] Excluído: ¶ Formatado ... [3] Excluído: ¶ Formatado ... [4] Formatado ... [5] Excluído: UNESP, Formatado ... [6] Excluído: and Formatado ... [7] Página 1: [1] Excluído Unknown Here, we use the eIF5AK56A and eIF5AQ22H/L93F mutants to investigate the relationship between eIF5A and eEF2. These eIF5A mutants are temperature-sensitive and show defect in protein synthesis as previously observed for eIF5A depletion, but eIF5AK56A and eIF5AQ22H/L93F proteins are stable at the restrictive temperature. Their main phenotypic difference is that eIF5AK56A has defect in hypusine modification. Although high-copy EFT2 (eEF2 encoding gene) is not able to complement the TIF51A (eIF5A encoding gene) knockout, the overproduction of eEF2 improves the cell growth of eIF5AK56A mutant and partially revert its protein synthesis and polysome profile defects at restrictive temperature, indicating a close functional relationship between eIF5A and eEF2. By contrast, eEF2 decrease the eIF5AQ22H/L93F growth and the protein synthesis rate at permissive or restrictive temperatures, revealing a synthetic sick phenotype. In order to investigate the ribosome-dependent physical interaction between eIF5A and eEF2, described before, we performed GST-pulldown assay using both cell extract and purified proteins. The hypusine defective mutant (eIF5AK56A) lost the interaction with the 80S ribosome, confirming previous results. However, the eIF5AQ22HL93F copurifies ribosomal proteins and binds directly to eEF2. Página 1: [2] Excluído Unknown for the first time a direct physical interaction between eIF5A and eEF2. Furthermore, the stronger binding between eIF5AQ22HL93F and eEF2 might be the cause of the growth and protein synthesis defects. Taken together, the different phenotypes showed by the two eIF5A mutants strongly suggest that eIF5A and eEF2 play a close role in the elongation step of protein synthesis Página 1: [3] Formatado fcf 14/6/2010 13:28:00 Fonte: Arial, Inglês (EUA) Página 1: [4] Formatado fcf 14/6/2010 13:53:00 Justificado, Espaçamento entre linhas: 1,5 linha Página 1: [5] Formatado fcf 14/6/2010 13:28:00 Fonte: Arial, Inglês (EUA) Página 1: [6] Formatado fcf 14/6/2010 13:28:00 Fonte: Arial, Inglês (EUA) Página 1: [7] Formatado fcf 14/6/2010 13:28:00 Fonte: Arial, Inglês (EUA) ��������������������������������������������������������������������������� ��������������������������������������������������������������������������������� �����������������������������������������������������.
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