Abstract
ABSTRACTTranslation is a key step in the regulation of gene expression and one of the most energy-consuming processes in the cell. In response to various stimuli, multiple signaling pathways converge on the translational machinery to regulate its function. To date, the roles of phosphoinositide 3-kinase (PI3K)/AKT and the mitogen-activated protein kinase (MAPK) pathways in the regulation of translation are among the best understood. Both pathways engage the mechanistic target of rapamycin (mTOR) to regulate a variety of components of the translational machinery. While these pathways regulate protein synthesis in homeostasis, their dysregulation results in aberrant translation leading to human diseases, including diabetes, neurological disorders, and cancer. Here we review the roles of the PI3K/AKT and MAPK pathways in the regulation of mRNA translation. We also highlight additional signaling mechanisms that have recently emerged as regulators of the translational apparatus.
Highlights
Translation is a key step in the regulation of gene expression and one of the most energy-consuming processes in the cell
Several mTORC1 substrates are involved in the regulation of mRNA translation, including the eukaryotic translation initiation factor 4E-binding proteins (4E-BPs), 70-kDa ribosomal S6 kinases (S6Ks) 1 and 2, and La-related protein 1 (LARP1) (La ribonucleoprotein domain family member 1) [23,24,25]
The functional role of rpS6 phosphorylation is largely unknown [148, 284]; these results suggest that ribosomal S6 kinases (RSKs) provides an mechanistic target of rapamycin (mTOR)/S6K-independent input linking mitogenactivated protein kinase (MAPK) signaling to the potential regulation of mRNA translation
Summary
Translation is a key step in the regulation of gene expression and one of the most energy-consuming processes in the cell. Several mTORC1 substrates are involved in the regulation of mRNA translation, including the eukaryotic translation initiation factor 4E (eIF4E)-binding proteins (4E-BPs), 70-kDa ribosomal S6 kinases (S6Ks) 1 and 2 (reviewed in references 20, 21, and 22), and LARP1 (La ribonucleoprotein domain family member 1) [23,24,25].
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