INITIATION OF PROTEIN-SYNTHESIS IN EUKARYOTES

The study of the regulation of initiation of protein synthesis has rec ently gained momentum because of the established relationship between translation initiation, cell growth and tumorigenesis. Therefore much effort is devoted to the role of protein kinases which are activated i n signal transduction cascades and which are responsible for the phosp horylation of a number of initiation factors. These specific factors a re mainly involved in the binding of messenger RNA to the 40S ribosome , a process that makes the unwinding of the 5' untranslated region nec essary. It appears that the phosphorylation of these factors increases their ability for cap recognition and helicase activity. The enhanced phosphorylation of the messenger binding factors results not only in an overall stimulation of translation, but especially weak messengers are positively discriminated. The above mechanisms mainly deal with qu alitative control of translation, i.e., messenger selection, but phosp horylation also plays a role in quantitative regulation of protein syn thesis. The generation of active eIF-2, the initiation factor that bin ds the Met-tRNA(i) and GTP, is dependent on a factor involved in the G DP-GTP exchange. Phosphorylation of eIF-2 results in sequestration of the exchange factor and a slowing down of the rate of initiation.