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Effects of novel C-methylated spermidine analogs on cell growth via hypusination of eukaryotic translation initiation factor 5A.
Hyvönen, Mervi T; Keinänen, Tuomo A; Khomutov, Maxim; Simonian, Alina; Vepsäläinen, Jouko; Park, Jong Hwan; Khomutov, Alex R; Alhonen, Leena; Park, Myung Hee.
Afiliação
  • Hyvönen MT; A.I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Yliopistonranta 1E, 70210, Kuopio, Finland. mervi.hyvonen@uef.fi
Amino Acids ; 42(2-3): 685-95, 2012 Feb.
Article em En | MEDLINE | ID: mdl-21861168
The polyamines, putrescine, spermidine, and spermine, are ubiquitous multifunctional cations essential for cellular proliferation. One specific function of spermidine in cell growth is its role as a butylamine donor for hypusine synthesis in the eukaryotic initiation factor 5A (eIF5A). Here, we report the ability of novel mono-methylated spermidine analogs (α-MeSpd, ß-MeSpd, γ-MeSpd, and ω-MeSpd) to function in the hypusination of eIF5A and in supporting the growth of DFMO-treated DU145 cells. We also tested them as substrates and inhibitors for deoxyhypusine synthase (DHS) in vitro. Of these compounds, α-MeSpd, ß-MeSpd, and γ-MeSpd (but not ω-MeSpd) were substrates for DHS in vitro, while they all inhibited the enzyme reaction. As racemic mixtures, only α-MeSpd and ß-MeSpd supported long-term growth (9-18 days) of spermidine-depleted DU145 cells, whereas γ-MeSpd and ω-MeSpd did not. The S-enantiomer of α-MeSpd, which supported long-term growth, was a good substrate for DHS in vitro, whereas the R-isomer was not. The long-term growth of DFMO-treated cells correlated with the hypusine modification of eIF5A by intracellular methylated spermidine analogs. These results underscore the critical requirement for hypusine modification in mammalian cell proliferation and provide new insights into the specificity of the deoxyhypusine synthase reaction.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Espermidina / Divisão Celular / Fatores de Iniciação de Peptídeos / Proteínas de Ligação a RNA / Lisina Limite: Humans / Male Idioma: En Revista: Amino Acids Assunto da revista: BIOQUIMICA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Finlândia País de publicação: Áustria

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Espermidina / Divisão Celular / Fatores de Iniciação de Peptídeos / Proteínas de Ligação a RNA / Lisina Limite: Humans / Male Idioma: En Revista: Amino Acids Assunto da revista: BIOQUIMICA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Finlândia País de publicação: Áustria