Translational control of the proteome: relevance to cancer

Abstract

Translational control is an important but relatively unappreciated mechanism that regulates levels of protein products. In addition to a global translational control that regulates the cell's response to external stimuli such as growth factors, cytokines, stress and viral infections, selective translational control has recently been demonstrated to affect many genes related to growth and apoptotic processes. Modifications in the 5'untranslated region of these specific mRNAs may lead to an up-regulation of the protein product by as much as 100-fold. Translational infidelity has been reported in some human cancers for oncogenes such as c-myc and mdm2. Furthermore, modulation of selective translational control has also been demonstrated in cells over-expressing the translation initiation factor elF4E. Elevated levels of elF4E were found in a broad spectrum of solid tumors (breast, head and neck, colon and bladder carcinomas as well as in non-Hodgkin's lymphomas). Other translation initiation factors and translation components such as elongation factors and ribosomal proteins have also been reported to be overexpressed in some human tumors. This review discusses the relevance of these observations to a cell's proteome and for tumorigenesis and how the genomics and proteomics can be used to advance our understanding of the role of translational control in cancer.