10 Translation Initiation and Cell Growth Control

Abstract

A great deal of research effort has been directed toward understanding the principles of cell growth. Growth and proliferation are tightly linked under most circumstances. Growth is defined as an increase in cell mass, and proliferation is defined as an increase in cell number. Cell growth consumes a large amount of energy due to the need for protein synthesis, which is the most energy-consuming process in the cell. Early work in yeast as well as more recent studies in mammals and Drosophila have established a critical link between cell growth and translational initiation. Furthermore, biological processes that require growth, such as cell division, differentiation, and development, are regulated at the translational level. Translation initiation is the primary target for translational control, and therefore it is implicated directly in the control of cell growth. A plethora of extracellular cues trigger the phosphorylation of several initiation factors in order to recruit ribosomes to the mRNA (Gingras et al. 1999a; Hershey and Merrick 2000). Changes in expression of the translational apparatus and dysregulation of its phosphorylation state cause dramatic changes in cell growth and often lead to diseases such as cancer (Hershey and Miyamoto 2000). This chapter describes how phosphorylation of translation initiation factors governs cell growth.

THE TRANSLATION INITIATION PATHWAY
Translation initiation in eukaryotes requires a large number of translation factors (~12) that promote the recruitment of ribosomes to the mRNA to form a translation initiation complex (for reviews, see Pain 1996; Hershey and Merrick 2000; Raught et al. 2000a). The initiation...