Translational control of gene expression: role of IRESs and consequences for cell transformation and angiogenesis.
Translational control of gene expression has, over the last 10 years, become appreciated as an important process in its regulation in eukaryotes. Among a series of control mechanisms exerted at the translational level, the use of alternative codons provides a very subtle means of increasing gene diversity by expressing several proteins from a single mRNA. The internal ribosome entry sites (IRESs) act as specific translational enhancers that allow translation initiation to occur independently of the classic cap-dependent mechanism, in response to specific stimuli and under the control of different trans-acting factors. It is striking to observe that the two processes mostly concern genes coding for control proteins such as growth factors, protooncogenes, angiogenesis factors, and apoptosis regulators. Here, we focus on the translational regulation of four mRNAs, with both IRESs and alternative initiation codons, which are the messengers of retroviral murine leukemia virus, fibroblast growth factor 2, vascular endothelial growth factor, and protooncogene c-myc. Four of them are involved in cell transformation and/or angiogenesis, with important consequences for such translation regulations in these pathophysiological processes.
Institut National de la Santé et de la Recherche Médicale U397, Endocrinologie et Communication Cellulaire, CHU Rangueil Toulouse, France.
Anne-Catherine
AC
Prats
Hervé
H
Prats
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002472:Cell Transformation, Viral; D018387:Codon, Initiator; D016228:Endothelial Growth Factors / Q000737:chemistry / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015685:Fusion Proteins, gag-pol / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D015967:Gene Expression Regulation, Viral; D016158:Genes, p53; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity; D008222:Lymphokines / Q000737:chemistry / Q000235:genetics; D014176:Protein Biosynthesis / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012315:RNA Caps; D012333:RNA, Messenger / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018387:Codon, Initiator; D016228:Endothelial Growth Factors; D015685:Fusion Proteins, gag-pol; D008222:Lymphokines; D016271:Proto-Oncogene Proteins c-myc; D012315:RNA Caps; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2