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 suggests that aberrant expression of growth-related genes by translational mechanisms makes a significant contribution to cell transformation. However, the mechanisms which regulate translation of specific growth-related mRNAs have yet to be fully elucidated. The majority of these mRNAs have long 5' untranslated regions (UTRs) and three features which are important in translational control have been identified, namely (i) structured regions which inhibit the scanning mechanisms of translation, (ii) regulatory upstream open reading frames and (iii) internal ribosome entry segments which are capable of initiating cap-independent translation. In this review the translational regulation of specific mRNAs encoding growth factors and proto-oncogenes by these three mechanisms will be discussed, together with examples of altered translational regulation in neoplasia.
Willis
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AE
Department of Biochemistry, University of Leicester, UK.
D020121:5' Untranslated Regions; D000818:Animals; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016258:Genes, mos; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2; D011519:Proto-Oncogenes / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; D006133:Growth Substances; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2