20 Translational Control and Cancer

Abstract

Cell growth is regulated by the carefully balanced expression of genes that either promote or inhibit cell proliferation. Cancerous cells arise when a number of these genes are mutated, thereby disturbing the balanced regulatory network. The stepwise accumulation of mutations that cause malignancy is thought to occur primarily in genes encoding growth factors, growth factor receptors, protein kinases involved in signal transduction cascades, and transcription factors (McCormick 1999). The genetic mutations, either inherited or generated by environmental factors such as irradiation, chemical carcinogens, and viral infection, cause dysregulation of cell growth and/or proliferation. In this chapter, we review the evidence supporting the notion that protein synthesis plays an important role in regulating cell proliferation and that aberrations in its regulation may contribute to loss of cell cycle control.

The cell cycle consists of a precisely regulated series of reactions or processes leading to cell growth and division. Protein synthesis and translational control of specific gene expression is required for the orderly transition from one phase of the cell cycle to the next. In yeast, for example, a conditional mutation in cdc33 encoding eIF4E causes arrest of cells at the G₁/S boundary, possibly due to inefficient synthesis of the cyclin CLN3 (Polymenis and Schmidt 1997; Danaie et al. 1999). Therefore, it is plausible that mutations in the genes encoding translational components that affect translational control could be oncogenic. The translational apparatus also is a target of signal transduction pathways that are activated by mitogens. Therefore, perturbations in signaling pathways that lead...