Translational control of the proteome: Relevance to cancer

Translational control is an important but relatively unappreciated mechanis m that regulates levels of protein products. In addition to a global transl ational control that regulates the cell's response to external stimuli such as growth factors, cytokines, stress and viral infections, selective trans lational control has recently been demonstrated to affect many genes relate d to growth and apoptotic processes. Modifications in the 5'untranslated re gion of these specific mRNAs may lead to an up-regulation of the protein pr oduct by as much as 100-fold. Translational infidelity has been reported in some human cancers for oncogenes such as c-myc and mdm2. Furthermore, modu lation of selective translational control has also been demonstrated in cel ls overexpressing the translation initiation factor elF4E. Elevated levels of elF4E were found in a broad spectrum of solid tumors (breast, head and n eck, colon and bladder carcinomas as well as in non-Hodgkin's lymphomas). O ther translation initiation factors and translation components such as elon gation factors and ribosomal proteins have also been reported to be overexp ressed in some human tumors. This review discusses the relevance of these o bservations 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 tra nslational control in cancer.