Translational control of growth factor and proto-oncogene expression

Control of translation is now understood to be one of the major regulatory events in eukaryotic gene expression. Moreover there is evidence which sugg ests that aberrant expression of growth-related genes by translational mech anisms makes a significant contribution to cell transformation. However, th e mechanisms which regulate translation of specific growth-related mRNAs ha ve yet to be fully elucidated. The majority of these mRNAs have long 5 ' un translated regions (UTRs) and three features which are important in transla tional control have been identified, namely (i) structured regions which in hibit the scanning mechanisms of translation, (ii) regulatory upstream open reading frames and (iii) internal ribosome entry segments which are capabl e of initiating cap-independent translation. Tn this review the translation al regulation of specific mRNAs encoding growth factors and proto-oncogenes by these three mechanisms will be discussed, together with examples of alt ered translational regulation in neoplasia. (C) 1999 Elsevier Science Ltd. All rights reserved.