High impact information on Eif5a

• Inhibition of cell growth through inactivation of eukaryotic translation initiation factor 5A (eIF5A) by deoxyspergualin [1].
• In the absence of spermidine synthesis, unhypusinated eukaryotic translation initiation factor 5A (eIF-5A) accumulated in AbeAdo-treated L1210 cells [2].
• Post-translational formation of hypusine in eukaryotic initiation factor 5A (eIF-5A) is essential for cell viability [3].
• In this report we suggest, for the first time, that tTGase affects hypusine metabolism, thus regulating the eIF-5A activity and cell proliferation [3].
• These results suggest that phosphorylation of deoxyhypusine synthase was PKC-dependent cellular event and open a path for possible regulation in the interaction with eIF5A precursor for hypusine synthesis [4].

Biological context of Eif5a

• The inhibition of cell growth and the formation of active eIF5A was not reversed by addition of spermidine [1].
• Hydroxylation of the deoxyhypusine residue completes hypusine formation on eIF-5A [5].

Anatomical context of Eif5a

• Hypusine formation on the eukaryotic initiation factor 5A (eIF-5A) precursor is ubiquitously present in eukaryotic cells and archebacteria [5].
• Despite the significant difference in eIF-5A protein amounts, the eIF-5A mRNA levels in 3T3 cells and in Ras-3T3 cells are almost identical [5].
• We have extended study on the phosphorylation of deoxyhypusine synthase in vivo in different cell lines in order to define its role on the regulation of eIF5A in the cell [4].
• Characterization and reconstitution of a cell free system for NAD(+)-dependent deoxyhypusine formation on the 18 kDa eIF-4D precursor [6].

Associations of Eif5a with chemical compounds

• These results, taken together, indicate that inhibition of active eIF5A formation is strongly involved in the inhibition of cell growth by deoxyspergualin [1].
• These results provide evidence that the formation of hypusine in the protein-synthesis initiation factor eIF-5A may be a critical role of spermidine essential for cell growth [7].
• However, spermine was able to rescue AbeAdo-treated L1210 cells without significantly reducing the unhypusinated eIF-5A accumulated during AbeAdo treatment, suggesting that only a small amount of the unmodified protein must be hypusinated to restore cell growth [2].
• Deoxyhpusine synthase catalyzes the conversion of lysine to deoxyhypusine residue on the eukaryotic initiation factor 5A (eIF-5A) precursor using spermidine as the substrate [8].
• The in vitro activity of deoxyhypusine formation, which depends on the presence of both enzyme and protein substrate, can be separated from the product, eIF-4D, by a one-step Cibacron blue dye affinity column [6].

Enzymatic interactions of Eif5a

• In this reaction, deoxyhypusine synthase catalyzes the conversion of one unique lysine residue on eIF-5A to deoxyhypusine using spermidine as the substrate [5].

Other interactions of Eif5a

• The large difference, >30-fold, in hypusine formation activity between these two cells is mainly due to difference in the amount of newly synthesized eIF-5A precursor rather than deoxyhypusine synthase [5].

References