About this Research Topic
This Research Topic provides the reader with the current status of some of the representative research projects dealing with the cap-independent translational control of carcinogenesis. Translational control of carcinogenesis, although still less well characterized than the transcriptional control of carcinogenesis, has recently been suggested to be the major contributor for cellular abundance of proteins. In the process of translation, a large number of accessory factors that assist the ribosome during initiation, elongation, and termination steps are required for protein synthesis. Consequently, the translational control of carcinogenesis can be influenced either positively or negatively by changing the level or the activity of rate-limiting protein factors taking part in the process of translation. Of the three steps of the translation process, initiation is the rate-limiting step and therefore the point at which much of the cellular translational control occurs. Translation initiation is often dysregulated during carcinogenesis. Translation initiation is affected by various stimuli that influence the phosphorylation status of eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs), which inhibit cap-dependent translation. Under conditions where cap-dependent translation is inhibited, translation of certain mRNA transcripts that tend to have a long-stretch of 5’-untranslated region (5’UTR) containing internal ribosome entry sites (IRESs) can still be supported in a cap-independent manner. Recently, the existence of additional pathways that are independent of 4E-PB1 phosphorylation pathways but can enhance cap-independent translation initiation of IRESs in the 5’UTR has been reported. These include modulation of other initiation factors, MAPK phosphorylation pathways, or methylation status of the 5’-cap of mRNAs, changes in intracellular ribosome levels, ribosomal RNA modifications, ribosomal proteins, or cellular proteins that modulate translation of specific mRNAs. The proteins synthesized using a cap-independent mechanism are involved in cancer cell growth, survival, and metastasis suggesting a significant role for translational control during carcinogenesis.
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